Personal Account
THE CHEMICAL RECORD
Boron Enolate Chemistry toward the Syntheses of Polyketide Stereotetrads Ari M. P. Koskinen*[a] Aalto University, School of Chemical Technology, Laboratory of Organic Chemistry, PO Box 16100, 00076 Aalto (Finland) E-mail: [email protected]
[a]
Received: September 29, 2013 Published online: January 13, 2014
ABSTRACT: In 1976 Mukaiyama published a paper that was to make a major impact on the development of the aldol reaction in the future. Mild enolate formation by treatment of a ketone with dibutylboron triflate in the presence of a tertiary amine generates a relatively stable boron enolate, which can subsequently react with an aldehyde to give the cross-aldol product in good yields. This reaction has become a reliable tool for the practicing synthetic chemist. Nearly 10000 polyketides are known, and of these about 600 contain the tripropionate unit with a stereotetrad, four contiguous stereocenters with alternating methyl and hydroxyl substituents in the main chain. The versatility of the boron enolate aldol reaction is showcased with selected applications in the synthesis of these structural motifs. DOI 10.1002/tcr.201300033 Keywords: aldol reaction, boron enolates, diastereoselectivity, enantioselectivity, polyketides
1. Introduction
Scheme 1. The original aldol reactions.
The acid-catalyzed self-condensation of acetone to give mesityl oxide was reported as early as 1838 by R. Kane (Scheme 1).[1]
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Alexander Borodin and Charles-Adolphe Wurtz independently recognized the product of an acid- or base-catalyzed reaction of acetaldehyde with itself to contain both an aldehyde and alcohol functionality in 1864 and 1872, respectively.[2] The reaction inherits its name from 3-hydroxybutanal, which Wurtz called aldol. Due to the power of aldol reactions to generate more complex organic structures from simple starting materials, aldol chemistry has become one of the most extensively studied reactions in organic synthesis.[3] The directed cross-aldol reaction of two different carbonyl compounds is an enormously powerful method to quickly and efficiently create stereochemically highly complex structures. The development of the Mukaiyama Ti aldol reaction has been recently summarized.[4] In 1976 Mukaiyama published a paper that was to make a major impact on the
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Fig. 1. Classification of stereotetrads.
Scheme 2. Mukaiyama boron enolate aldol reaction.
development of the aldol reaction in the future (Scheme 2).[5] Mild enolate formation by treatment of a ketone with dibutylboron triflate in the presence of a tertiary amine generates a relatively stable boron enolate,[6] which can subsequently react with an aldehyde to give the cross-aldol product in good yields. This reaction has become a reliable tool for the practicing synthetic chemist.[7] This account illustrates the use of the boron enolate– mediated aldol reaction for the synthesis of polyketides. The
Ari M. P. Koskinen (1956) received his M.Sc. (Chem. Eng.) in 1979 and Doctor of Technology (with Prof. M. Lounasmaa) in 1983 at the Helsinki University of Technology, Finland. After postdoctoral studies at the University of California, Berkeley (with Prof. Henry Rapoport), he worked as a Project Leader in New Drug Development at Orion Corporation—Fermion, Finland (1985–1987). Returning to academia, he joined the University of Surrey, England, as a lecturer in 1989. He was appointed as Professor of Chemistry at the University of Oulu, Finland, in 1992, and moved to his current position at the Helsinki University of Technology (Aalto University since 2011) in August 1999 as Professor of Organic Chemistry (the old Gustav Komppa chair). Prof. Koskinen has been a member of the Finnish Academy of Sciences and Letters since 2003. He is the author or co-author of some 170 publications, ten patents and two books.
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emphasis is on the scope of the reaction for the synthesis of a particularly attractive and rich structural element in natural products, with no intention to cover the literature extensively. The choice of the examples is personal, and I apologize for the omission of several beautiful examples due to lack of space. The concept of aldol products in natural products has evolved hand in hand together with the progression of our understanding of asymmetric synthesis. Treatises on natural product chemistry from the 1950s to the early 1970s mainly dealt with “acetogenins”, whose molecular skeletons were constructed via aldol-type condensations. The compound classes of interest were mainly fatty acid derivatives and aromatic compounds (e.g., phloroglucinols, chromones, and flavonoids). Few polypropionates were known, and it was even stated, “It is convenient to include here for survey purposes a number of small structure groups of obscure biogenesis, which nonetheless appear related to acetogenins . . . it is surprising how very few seriously anomalous structures are to be found among natural products.”[8] Only a few macrolides were known then. The advent of spectroscopic structure elucidation methods, together with chromatographic purification methods, soon led to increasing numbers of more and more complex natural product structures becoming available, and this rapid growth was further augmented by the development of the concepts and practices of stereochemistry and asymmetric synthesis starting roughly from the 1970s. Today nearly 10000 polyketides are known, and of them about 600 contain the tripropionate unit with a stereotetrad, four contiguous stereocenters with alternating methyl and hydroxyl substituents in the main chain. On the basis of their relative stereochemistry these can be classified in the eight structural types shown in Figure 1 (only one set of enantiomers is shown). One should bear in mind that the biosynthesis of polyketides is not based on the aldol reaction, but on a Claisen-type condensation producing a β-keto ester followed by reduction to give the hydroxyacid derivative.[9] In the following text, the application of the boron enolate aldol reaction towards these structural types will be discussed.
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2. Stereotetrad Syntheses by Type Type 1—anti, anti, anti Polyether antibiotics characteristically contain a carboxylate group and a number of additional oxygen ligands, which make these compounds highly effective in complexing inorganic cations. The derived complexes are highly hydrophobic, and thereby facilitate translocation of ions across membranes, hence their common name “ionophores”. Ionomycin (Figure 2) was
Fig. 2. Type 1 stereotetrad with anti, anti, anti stereochemistry: ionomycin.
isolated from Streptomyces conglobatus as its hexane-soluble calcium salt by Meyers in 1978,[10] and has gained widespread use as a research tool to understand Ca2+ transport across membranes. Ionomycin contains altogether 14 stereocenters and their selective construction posed formidable challenges, especially for the development of aldol technology. Segment C18– C21 contains a type 1 dipropionate unit with anti, anti, anti stereochemistry. The synthesis of this unit employing the highly stereoselective boron enolate aldol methodology was reported by Evans in connection with the total synthesis of ionomycin in 1990 (Scheme 3).[11] The norephedrine-derived crotonoyloxazolidinone was first transformed to the (Z)–dibutylboron enolate to ensure syn selectivity in the aldol process. Reaction with the (R)-Roche aldehyde ((R)3-benzyloxy-2-methylpropanal)[12] then proceeded with high antiFelkin–Anh diastereoselectivity giving the syn, anti product.[13] In a clever tactical move, after suitable reductive operations involving deoxygenation, the original carbonyl group became a surrogate for the methyl group, thus effectively reversing the apparent diastereoselectivity to give the desired anti, anti product. The vinyl
Scheme 3. Evans synthesis of the C18–C21 fragment of ionomycin.
Fig. 3. Transition-state model.
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group was eventually converted oxidatively to the C21 methine, whose stereochemistry was secured at the ketal aldehyde stage by equilibration to the most stable isomer with all equatorial substituents (shown). The anti-Felkin–Anh diastereoselectivity is explained with the cyclic Zimmerman–Traxler-like transition-state model in Figure 3. The ephedrine-derived chiral auxiliary orients the (Z)–boron enolate so as to accept the aldehyde electrophile from behind the plane of the
paper. This orientation is facilitated by placing the C–O–B and N–C=O dipoles opposite to each other. The aldehyde electrophile orients itself so that the side chain is equatorial in the six-membered transition state, and the α-carbon atom substituents occupy the positions shown, so that the largest substituent is furthest away from the nucleophile and the smallest substituent (H) occupies the most sterically shielded space. Thus, high anti-Felkin–Anh and syn selectivities are achieved.
Fig. 4. Type 2 (anti, anti, syn) and type 3 (anti, syn, anti) stereotetrads: aplyronines.
Scheme 4. Paterson synthesis of the C21–C34 fragment of aplyronine A.
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Type 2—anti, anti, syn Both type 2 (anti, anti, syn) and type 3 (anti, syn, anti) stereotetrads occur in the structure of aplyronines, and in fact the latter anti, syn, anti occurs in both enantiomeric forms
Scheme 5. Yamada synthesis of the C5–C11 segment of aplyronine A.
(Figure 4). Aplyronines are 24-membered macrolide antibiotics with marked cytotoxic and apoptotic activities.[14] They were originally isolated by Yamada from marine sea hares Aplysia kurodai,[15] and have gained widespread synthetic interest because of their intriguing physiological activities that include antiproliferative properties.[16] Synthesis of the two type 2 stereotetrads C23–C26 and C29–C32 using boron enolate aldol reactions was achieved by Paterson (Scheme 4).[17] The lactate-derived ethyl ketone was enolized with dicyclohexylboron chloride and diethylmethylamine to give the corresponding (E)-enolate to ensure anti selectivity for the aldol reaction. Reaction with the PMBprotected (S)-Roche aldehyde analogue gave the anti, anti product. In a sequence involving several steps this was converted to phosphonate A for coupling with aldehyde B, which contains the “enantiomeric” type 2 stereotetrad. This was synthesized based on the tin(II)-promoted aldol reaction, another technology pioneered by Mukaiyama.[18] After coupling of the two fragments the final stereochemistry at C29 was set with an Evans–Tishchenko reduction.[19]
Scheme 6. Paterson synthesis of the C1–C11 segment of aplyronine A.
Scheme 7. Attempted synthesis of a calyculin segment.
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Type 3—anti, syn, anti
Type 4—syn, anti, anti
The structure of aplyronines also contains one type 3 stereotetrad (C7–C10). Yamada confirmed the absolute stereochemistry of aplyronines by total synthesis.[20] This included the construction of the C5–C11 segment of aplyronine A, which began with an Evans aldol reaction between the propionate imide (Scheme 5)[21] and (R)-Roche aldehyde giving the syn, anti product as in the previous synthesis of ionomycin. The aldol product was elaborated to an allyl alcohol, whose Sharpless asymmetric epoxidation[22] followed by reductive cleavage of the epoxide ring with Red-Al[23] gave the targeted segment with the anti, syn, anti stereochemistry. Paterson’s approach to the synthesis of this segment is shown in Scheme 6.[24] The (R)-Roche ester–derived ethyl ketone was first converted to the (E)–boron enolate with dicyclohexylboron chloride and an aldol reaction with the long-chain ynoate aldehyde gave the desired anti, anti aldol adduct in 96% yield with ≥97% ds. The stereochemistry at C9 was set through an Evans–Tishchenko reduction.
In connection with a project aimed at a total synthesis of calyculin, we investigated a boron enolate–mediated aldol reaction followed by Narasaka–Pai stereodirected reduction[25] to construct a polypropionate segment C10–C13 with an anti, anti, anti stereochemistry. In the event, the product turned out to have the syn, anti, anti stereochemistry.[26] This unanticipated stereochemical result can be rationalized by the boxed model shown in Scheme 7. Though not conducive to our original synthetic plan, this prompted us to endeavor toward the synthesis of another natural product, amphotericin B. Amphotericin B (AmB), produced by Streptomyces nodosus,[27] is one of the most prominent members of the clinically important polyene macrolides.[28] It is widely used as an antifungal agent, and serves as the drug of choice in the clinic for antifungal chemotherapy in life-threatening infections.[29] The C33–C37 fragment of amphotericin B (boxed in Figure 5) is a tripropionate segment containing four contiguous stereocenters with type 4 syn, anti, anti stereochemistry. Our own synthesis of the C33–C37 fragment of AmB commenced with a chiral orthoester derived from l-tartrate which reacted with the silyl enol ether of thiopyranone to give a chiral formylthiopyranone equivalent (Scheme 8).[30] Its silyl enol ether reacted with acetaldehyde in a titanium-catalyzed Mukaiyama aldol reaction to furnish the fragment with three
Fig. 5. Type 4 stereotetrad with syn, anti, anti stereochemistry: amphotericin B.
Fig. 6. Type 6 stereotetrad with syn, anti, syn stereochemistry: pironetin.
Scheme 8. Koskinen synthesis of the amphotericin B C33–C37 fragment.
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stereocenters correctly set. Final steps included a stereodirected reduction of the hydroxyketone to set the final stereocenter, and reductive desulfurization with Raney nickel. The synthesis of the C33–C37 fragment involves only six steps from l-tartrate and scales up readily. Type 6—syn, anti, syn Pironetin or PA-48153C is an unsaturated δ-lactone derivative isolated from Streptomyces species.[31] It possesses plant growth regulatory properties as well as immunosuppressive activity, which is manifested through a pathway different from the established immunosuppressants cyclosporin A and FK506. Pironetin contains a type 6 syn, anti, syn stereotetrad at C7–C10 (boxed in Figure 6). The innate syn aldol selectivity of the (Z)–dibutylboron enolate was again utilized twice in the synthesis of the pironetin syn, anti, syn fragment by Dias (Scheme 9).[32] Thus, the dibutylboron enolate of the (S)-oxazolidinone was first reacted with the hydroxypropionaldehyde derivative to set the C9 and C10 stereochemistries. After conversion of the
oxazolidinoyl chiral auxiliary to an aldehyde function through the Weinreb amide, a second Evans aldol reaction with the (R)-oxazolidinone–derived dibutylboron enolate gave the C7 and C8 stereocenters in a syn fashion. The 8,9-anti relationship was gained in >95:5 diastereoselectivity, testifying to the efficient reagent control by the Evans chiral auxiliary to override Felkin selectivity in the addition step. Type 7—anti, syn, syn Immunosuppressing agents have received enormous attention during the past two decades, and novel modes of action have enabled the investigation of several new structural classes of natural products exhibiting immunosuppressive activity. Stevastelins (Figure 7), one such novel group, were originally isolated from culture broths of Penicillium sp. NK374186.[33] Stevastelins are depsipeptides which contain a substituted stearic acid subunit incorporating a type 7 anti, syn, syn stereotetrad propionate unit. Sarabia et al. began the synthesis of the stereotetrad of stevastelins with the Evans aldol methodology to create the first
Scheme 9. Dias synthesis of the C6–C12 segment of pironetin.
Fig. 7. Type 7 stereotetrad with anti, syn, syn stereochemistry: stevastelins.
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two stereocenters in a syn manner (Scheme 10).[34] The other two stereocenters were created via a second aldol reaction of the (E)–boron enolate of t-butyl thiopropionate and the chiral aldehyde. Only one diastereomer, the desired anti, syn, syn product was obtained, following Felkin–Anh selectivity. Type 8—syn, syn, syn Erythromycins and erythronolides (Figure 8) and their derivatives are among the earliest and by far the most extensively studied macrolide antibiotics (more than 50 000 references at the time of writing this review). Erythromycin A was isolated in the early 1950s from a strain of Saccharopolyspora erythraea (Streptomyces erythraeus),[35] and its complete structure was revealed in 1965 by X-ray analysis. The antibiotic activity of erythromycins is related to their ability to inhibit ribosomaldependent protein biosynthesis.[36]
The structure of erythromycin was deemed “hopelessly complex, particularly in view of its plethora of asymmetric centers,”[37] and for over four decades the challenging structures of erythromycins and erythronolides attracted many research groups, but surprisingly few total syntheses have been reported.[38] The C2–C5 fragment of erythromycins contains a type 8 all-syn stereotetrad (boxed in Figure 8). A total synthesis of erythromycins published in 2003 by Martin et al. (Scheme 11)[39] involved the synthesis of the syn, syn, syn stereotetrad fragment. The synthesis started with an Evans aldol reaction of a (Z)–boron enolate to give the syn aldol adduct as the only isomer. After several reaction steps, which concentrated on the synthesis of the left half of erythromycin B, two missing stereocenters of the syn, syn, syn stereotetrad were created via asymmetric crotylation.
3. Conclusions Figure 9 shows a summary of the polyketide types synthesized and discussed in this text. The versatility of the Mukaiyama
Scheme 10. Sarabia synthesis of a stevastelin segment.
Fig. 8. Type 8 stereotetrad with syn, syn, syn stereochemistry: erythromycin B.
Scheme 11. Martin synthesis of the erythromycin B stereotetrad C2–C5.
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Fig. 9. Stereotetrad types synthesized using the boron enolate aldol reaction.
boron-mediated aldol reaction is evident: all structural classes, except type 5, have been synthesized with this methodology. Type 5 represents an exception, and deserves a comment that points out an interesting feature in the overall scenario. It turns out that this stereotetrad type is very rare in nature, occurring in only a few natural products.[40] No syntheses involving the aldol strategy have been reported so far. The boron enolate aldol strategy has proven its versatility in the syntheses of polyketide stereotetrads, and the outlook for further developments is promising. New developments for more elaborate structures, catalytic enolization methods and asymmetric induction protocols will undoubtedly broaden the scope of this powerful technology even further.
[8]
[9] [10] [11] [12]
[13] [14]
REFERENCES [1] [2]
[3]
[4] [5] [6] [7]
a) R. Kane, Ann. Phys. 1838, 120, 473–494; b) R. Kane, J. Prakt. Chem. 1838, 15, 129–155. a) A. Borodin, J. Prakt. Chem. 1864, 93, 413–425; b) A. Wurtz, Bull. Soc. Chim. Fr. 1872, 17, 436–442; c) A. Wurtz, J. Prakt. Chem. 1872, 5, 457–464; d) A. Wurtz, C. R. Hebd. Seances Acad. Sci. 1872, 74, 1361–1367; e) A. Wurtz, Chem. Ber. 1872, 5, 326–327. For leading general reviews on the aldol reaction, see e.g., a) A. T. Nielsen, W. T. Houlihan, Org. React. 1968, 16, 1–438; b) T. Mukaiyama, Org. React. 1982, 28, 203–331; c) B. Schetter, R. Mahrwald, Angew. Chem., Int. Ed. 2006, 45, 7506–7525; d) E. M. Carreira, A. Fettes, C. Marti, Org. React. 2006, 67, 1–216. J. Matsuo, M. Murakami, Angew. Chem., Int. Ed. 2013, 52, 9109–9118. T. Mukaiyama, T. Inoue, Chem. Lett. 1976, 5, 559–562. T. Mukaiyama, K. Inomata, Bull. Chem. Soc. Jpn. 1971, 44, 3215. For reviews, see: a) C. J. Cowden, I. Paterson, Org. React. 1997, 51, 1–200; b) T. Mukaiyama, J.-I. Matsuo, in Modern Aldol
60 www.tcr.wiley-vch.de
[15] [16] [17] [18]
[19] [20]
[21] [22]
Chem. Rec. 2014, 14, 52–61
Reactions (Ed.: R. Mahrwald), Wiley-VCH, Weinheim, Germany, 2008. J. B. Hendrickson, The Molecules of Nature: A Survey of the Biosynthesis and Chemistry of Natural Products, BenjaminCummings Publishing Company, Reading, Massachusetts, 1965, p. 33. For a recent review on polyketide biosynthesis, see C. Hertweck, Angew. Chem., Int. Ed. 2009, 48, 4688–4716. W.-C. Liu, D. Smith-Slusarchyk, G. Astle, W. H. Trejo, W. E. Brown, E. Meyers, J. Antibiot. 1978, 31, 815–819. D. A. Evans, R. L. Dow, T. L. Shih, J. M. Takacs, R. Zahler, J. Am. Chem. Soc. 1990, 112, 5290–5313. A. I. Meyers, K. A. Babiak, A. L. Campbell, D. L. Comins, M. P. Fleming, R. Henning, M. Heuschmann, J. P. Hudspeth, J. M. Kane, P. J. Reider, D. M. Roland, K. Shimizu, K. Tomioka, R. D. Walkup, J. Am. Chem. Soc. 1983, 105, 5015–5024. D. A. Evans, E. B. Sjogren, J. Bartroli, R. L. Dow, Tetrahedron Lett. 1986, 27, 4957–4960. K. Yamada, M. Ojika, H. Kigoshi, K. Suenaga, Nat. Prod. Rep. 2009, 26, 27–43. K. Yamada, M. Ojika, T. Ishigaki, Y. Yoshida, H. Ekimoto, M. Arakawa, J. Am. Chem. Soc. 1993, 115, 11020–11021. For a review on actin-binding macrolides, see: K. S. Yeung, I. Paterson, Angew. Chem., Int. Ed. 2002, 41, 4632–4653. I. Paterson, S. B. Blakey, C. J. Cowden, Tetrahedron Lett. 2002, 43, 6005–6008. a) T. Mukaiyama, R. W. Stevens, N. Iwasawa, Chem. Lett. 1982, 11, 353—356; b) T. Mukaiyama, N. Iwasawa, Chem. Lett. 1982, 11, 1903–1906. D. A. Evans, A. H. Hoveyda, J. Am. Chem. Soc. 1990, 112, 6447–6449. a) H. Kigoshi, M. Ojika, T. Ishigaki, K. Suenaga, T. Mutou, A. Sakakura, T. Ogawa, K. Yamada, J. Am. Chem. Soc. 1994, 116, 1443–1444; b) H. Kigoshi, K. Suenaga, T. Mutou, T. Ishigaki, T. Atsumi, H. Ishiwata, A. Sakakura, T. Ogawa, M. Ojika, K. Yamada, J. Org. Chem. 1996, 61, 5326–5351. D. A. Evans, J. Bartroli, T. L. Shih, J. Am. Chem. Soc. 1981, 103, 2127–2129. T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974–5976.
© 2014 The Chemical Society of Japan and Wiley-VCH, Weinheim
B o ro n En o l a t e s i n Po l y k e t i d e St e re o t e t r a d Sy n t h e s i s
[23]
[24] [25] [26] [27] [28] [29] [30] [31]
[32] [33]
a) J. M. Finan, Y. Kishi, Tetrahedron Lett. 1982, 23, 2719– 2722; b) K. C. Nicolaou, J. Uenishi, J. Chem. Soc., Chem. Commun. 1982, 1292–1293. I. Paterson, C. J. Cowden, M. D. Woodrow, Tetrahedron Lett. 1998, 39, 6037–6040. K. Narasaka, F. C. Pai, Chem. Lett. 1980, 9, 1415–1418. K. Karisalmi, A. M. P. Koskinen, Synthesis 2004, 1331–1342. H. A. B. Linke, W. Mechlinski, C. P. Schaffner, J. Antibiot. 1974, 27, 155–160. Macrolide Antibiotics: Chemistry, Biology and Practice (Ed.: S. Omura), Academic Press, New York, 1984. P. A. Hunter, Drug Discovery Today 1996, 1, 227–228. K. Karisalmi, K. Rissanen, A. M. P. Koskinen, Org. Biomol. Chem. 2003, 1, 3193–3196. a) S. Kobayashi, K. Tsuchiya, T. Harada, M. Nishide, T. Kurokawa, T. Nakagawa, N. Shimada, K. Kobayashi, J. Antibiot. 1994, 47, 697–702; b) S. Kobayashi, K. Tsuchiya, T. Kurokawa, T. Nakagawa, N. Shimada, Y. Iitaka, J. Antibiot. 1994, 47, 703–707; c) T. Yoshida, K. Koizumi, Y. Kawamura, K. Matsumoto, H. Itazaki, Eur. Pat. Appl. 560389 A1, 1993; d) K. Yasui, Y. Tamura, T. Nakatani, K. Kawada, M. Ohtani, J. Org. Chem. 1995, 60, 7567–7674. L. C. Dias, L. G. Oliveira, M. A. de Sousa, Org. Lett. 2003, 5, 265–268. a) T. Morino, A. Masuda, M. Yamada, M. Nishimoto, T. Nishikori, S. Saito, N. Shimada, J. Antibiot. 1994, 47, 1341– 1343; b) T. Morino, K.-I. Shimada, A. Masuda, M. Nishimoto, S. Saito, J. Antibiot. 1996, 49, 1049–1051.
Chem. Rec. 2014, 14, 52–61
[34] [35]
[36] [37] [38] [39]
[40]
F. Sarabia, S. Chammaa, F. J. López-Herrera, Tetrahedron Lett. 2002, 43, 2961–2965. J. M. McGuire, R. L. Bunch, R. C. Anderson, H. E. Boaz, E. H. Flynn, H. M. Powell, J. W. Smith, Antibiot. Chemother. (Washington, D. C.) 1952, 2, 281–283. a) S. Pal, Tetrahedron 2006, 62, 3171–3200; b) B. Vester, S. Douthwaite, Antimicrob. Agents Chemother. 2001, 45, 1–12. R. B. Woodward in Perspectives in Organic Chemistry (Ed.: A. R. Todd), Interscience, New York, 1956, p. 160. For a review, see: X. Gao, S. K. Woo, M. J. Krische, J. Am. Chem. Soc. 2013, 135, 4223−4226. a) S. F. Martin, W.-C. Lee, G. J. Pacofsky, R. P. Gist, T. A. Mulhern, J. Am. Chem. Soc. 1994, 116, 4674–4688; b) P. J. Hergenrother, A. Hodgson, A. S. Judd, W.-C. Lee, S. F. Martin, Angew. Chem., Int. Ed. 2003, 42, 3278–3281; c) P. Breton, P. J. Hergenrother, T. Hida, A. Hodgson, A. S. Judd, E. Kraynack, P. R. Kym, W.-C. Lee, M. S. Loft, M. Yamashita, S. F. Martin, Tetrahedron 2007, 63, 5709–5729. Lankamycin and lankacidin: a) E. Gaumann, R. Hutter, W. Keller-Schierlein, L. Neipp, V. Prelog, H. Zahner, Helv. Chim. Acta 1960, 43, 601–606. Portmicin: b) R. L. Hamill, R. C. Yao, U.S. Patent 4,582,822, 1986; c) Y. Kusakabe, N. Takahashi, Y. Iwagaya, A. Seino, J. Antibiot. 1987, 40, 237–238. Enteridinine: d) T. Rezanka, R. Dvorˇáková, L. O. Hanuš, V. M. Dembitsky, Phytochemistry 2004, 65, 455–462. Langkolide: e) S. E. Helaly, A. Kulik, H. Zinecker, K. Ramachandaran, G. Y. A. Tan, J. F. Imhoff, R. D. Suessmuth, H.-P. Fiedler, V. Sabaratnam, J. Nat. Prod. 2012, 75, 1018–1024.
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Boron Enolate Chemistry toward the Syntheses of Polyketide Stereotetrads Ari M. P. Koskinen*[a] Aalto University, School of Chemical Technology, Laboratory of Organic Chemistry, PO Box 16100, 00076 Aalto (Finland) E-mail: [email protected]
[a]
Received: September 29, 2013 Published online: January 13, 2014
ABSTRACT: In 1976 Mukaiyama published a paper that was to make a major impact on the development of the aldol reaction in the future. Mild enolate formation by treatment of a ketone with dibutylboron triflate in the presence of a tertiary amine generates a relatively stable boron enolate, which can subsequently react with an aldehyde to give the cross-aldol product in good yields. This reaction has become a reliable tool for the practicing synthetic chemist. Nearly 10000 polyketides are known, and of these about 600 contain the tripropionate unit with a stereotetrad, four contiguous stereocenters with alternating methyl and hydroxyl substituents in the main chain. The versatility of the boron enolate aldol reaction is showcased with selected applications in the synthesis of these structural motifs. DOI 10.1002/tcr.201300033 Keywords: aldol reaction, boron enolates, diastereoselectivity, enantioselectivity, polyketides
1. Introduction
Scheme 1. The original aldol reactions.
The acid-catalyzed self-condensation of acetone to give mesityl oxide was reported as early as 1838 by R. Kane (Scheme 1).[1]
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Alexander Borodin and Charles-Adolphe Wurtz independently recognized the product of an acid- or base-catalyzed reaction of acetaldehyde with itself to contain both an aldehyde and alcohol functionality in 1864 and 1872, respectively.[2] The reaction inherits its name from 3-hydroxybutanal, which Wurtz called aldol. Due to the power of aldol reactions to generate more complex organic structures from simple starting materials, aldol chemistry has become one of the most extensively studied reactions in organic synthesis.[3] The directed cross-aldol reaction of two different carbonyl compounds is an enormously powerful method to quickly and efficiently create stereochemically highly complex structures. The development of the Mukaiyama Ti aldol reaction has been recently summarized.[4] In 1976 Mukaiyama published a paper that was to make a major impact on the
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Fig. 1. Classification of stereotetrads.
Scheme 2. Mukaiyama boron enolate aldol reaction.
development of the aldol reaction in the future (Scheme 2).[5] Mild enolate formation by treatment of a ketone with dibutylboron triflate in the presence of a tertiary amine generates a relatively stable boron enolate,[6] which can subsequently react with an aldehyde to give the cross-aldol product in good yields. This reaction has become a reliable tool for the practicing synthetic chemist.[7] This account illustrates the use of the boron enolate– mediated aldol reaction for the synthesis of polyketides. The
Ari M. P. Koskinen (1956) received his M.Sc. (Chem. Eng.) in 1979 and Doctor of Technology (with Prof. M. Lounasmaa) in 1983 at the Helsinki University of Technology, Finland. After postdoctoral studies at the University of California, Berkeley (with Prof. Henry Rapoport), he worked as a Project Leader in New Drug Development at Orion Corporation—Fermion, Finland (1985–1987). Returning to academia, he joined the University of Surrey, England, as a lecturer in 1989. He was appointed as Professor of Chemistry at the University of Oulu, Finland, in 1992, and moved to his current position at the Helsinki University of Technology (Aalto University since 2011) in August 1999 as Professor of Organic Chemistry (the old Gustav Komppa chair). Prof. Koskinen has been a member of the Finnish Academy of Sciences and Letters since 2003. He is the author or co-author of some 170 publications, ten patents and two books.
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emphasis is on the scope of the reaction for the synthesis of a particularly attractive and rich structural element in natural products, with no intention to cover the literature extensively. The choice of the examples is personal, and I apologize for the omission of several beautiful examples due to lack of space. The concept of aldol products in natural products has evolved hand in hand together with the progression of our understanding of asymmetric synthesis. Treatises on natural product chemistry from the 1950s to the early 1970s mainly dealt with “acetogenins”, whose molecular skeletons were constructed via aldol-type condensations. The compound classes of interest were mainly fatty acid derivatives and aromatic compounds (e.g., phloroglucinols, chromones, and flavonoids). Few polypropionates were known, and it was even stated, “It is convenient to include here for survey purposes a number of small structure groups of obscure biogenesis, which nonetheless appear related to acetogenins . . . it is surprising how very few seriously anomalous structures are to be found among natural products.”[8] Only a few macrolides were known then. The advent of spectroscopic structure elucidation methods, together with chromatographic purification methods, soon led to increasing numbers of more and more complex natural product structures becoming available, and this rapid growth was further augmented by the development of the concepts and practices of stereochemistry and asymmetric synthesis starting roughly from the 1970s. Today nearly 10000 polyketides are known, and of them about 600 contain the tripropionate unit with a stereotetrad, four contiguous stereocenters with alternating methyl and hydroxyl substituents in the main chain. On the basis of their relative stereochemistry these can be classified in the eight structural types shown in Figure 1 (only one set of enantiomers is shown). One should bear in mind that the biosynthesis of polyketides is not based on the aldol reaction, but on a Claisen-type condensation producing a β-keto ester followed by reduction to give the hydroxyacid derivative.[9] In the following text, the application of the boron enolate aldol reaction towards these structural types will be discussed.
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2. Stereotetrad Syntheses by Type Type 1—anti, anti, anti Polyether antibiotics characteristically contain a carboxylate group and a number of additional oxygen ligands, which make these compounds highly effective in complexing inorganic cations. The derived complexes are highly hydrophobic, and thereby facilitate translocation of ions across membranes, hence their common name “ionophores”. Ionomycin (Figure 2) was
Fig. 2. Type 1 stereotetrad with anti, anti, anti stereochemistry: ionomycin.
isolated from Streptomyces conglobatus as its hexane-soluble calcium salt by Meyers in 1978,[10] and has gained widespread use as a research tool to understand Ca2+ transport across membranes. Ionomycin contains altogether 14 stereocenters and their selective construction posed formidable challenges, especially for the development of aldol technology. Segment C18– C21 contains a type 1 dipropionate unit with anti, anti, anti stereochemistry. The synthesis of this unit employing the highly stereoselective boron enolate aldol methodology was reported by Evans in connection with the total synthesis of ionomycin in 1990 (Scheme 3).[11] The norephedrine-derived crotonoyloxazolidinone was first transformed to the (Z)–dibutylboron enolate to ensure syn selectivity in the aldol process. Reaction with the (R)-Roche aldehyde ((R)3-benzyloxy-2-methylpropanal)[12] then proceeded with high antiFelkin–Anh diastereoselectivity giving the syn, anti product.[13] In a clever tactical move, after suitable reductive operations involving deoxygenation, the original carbonyl group became a surrogate for the methyl group, thus effectively reversing the apparent diastereoselectivity to give the desired anti, anti product. The vinyl
Scheme 3. Evans synthesis of the C18–C21 fragment of ionomycin.
Fig. 3. Transition-state model.
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group was eventually converted oxidatively to the C21 methine, whose stereochemistry was secured at the ketal aldehyde stage by equilibration to the most stable isomer with all equatorial substituents (shown). The anti-Felkin–Anh diastereoselectivity is explained with the cyclic Zimmerman–Traxler-like transition-state model in Figure 3. The ephedrine-derived chiral auxiliary orients the (Z)–boron enolate so as to accept the aldehyde electrophile from behind the plane of the
paper. This orientation is facilitated by placing the C–O–B and N–C=O dipoles opposite to each other. The aldehyde electrophile orients itself so that the side chain is equatorial in the six-membered transition state, and the α-carbon atom substituents occupy the positions shown, so that the largest substituent is furthest away from the nucleophile and the smallest substituent (H) occupies the most sterically shielded space. Thus, high anti-Felkin–Anh and syn selectivities are achieved.
Fig. 4. Type 2 (anti, anti, syn) and type 3 (anti, syn, anti) stereotetrads: aplyronines.
Scheme 4. Paterson synthesis of the C21–C34 fragment of aplyronine A.
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Type 2—anti, anti, syn Both type 2 (anti, anti, syn) and type 3 (anti, syn, anti) stereotetrads occur in the structure of aplyronines, and in fact the latter anti, syn, anti occurs in both enantiomeric forms
Scheme 5. Yamada synthesis of the C5–C11 segment of aplyronine A.
(Figure 4). Aplyronines are 24-membered macrolide antibiotics with marked cytotoxic and apoptotic activities.[14] They were originally isolated by Yamada from marine sea hares Aplysia kurodai,[15] and have gained widespread synthetic interest because of their intriguing physiological activities that include antiproliferative properties.[16] Synthesis of the two type 2 stereotetrads C23–C26 and C29–C32 using boron enolate aldol reactions was achieved by Paterson (Scheme 4).[17] The lactate-derived ethyl ketone was enolized with dicyclohexylboron chloride and diethylmethylamine to give the corresponding (E)-enolate to ensure anti selectivity for the aldol reaction. Reaction with the PMBprotected (S)-Roche aldehyde analogue gave the anti, anti product. In a sequence involving several steps this was converted to phosphonate A for coupling with aldehyde B, which contains the “enantiomeric” type 2 stereotetrad. This was synthesized based on the tin(II)-promoted aldol reaction, another technology pioneered by Mukaiyama.[18] After coupling of the two fragments the final stereochemistry at C29 was set with an Evans–Tishchenko reduction.[19]
Scheme 6. Paterson synthesis of the C1–C11 segment of aplyronine A.
Scheme 7. Attempted synthesis of a calyculin segment.
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Type 3—anti, syn, anti
Type 4—syn, anti, anti
The structure of aplyronines also contains one type 3 stereotetrad (C7–C10). Yamada confirmed the absolute stereochemistry of aplyronines by total synthesis.[20] This included the construction of the C5–C11 segment of aplyronine A, which began with an Evans aldol reaction between the propionate imide (Scheme 5)[21] and (R)-Roche aldehyde giving the syn, anti product as in the previous synthesis of ionomycin. The aldol product was elaborated to an allyl alcohol, whose Sharpless asymmetric epoxidation[22] followed by reductive cleavage of the epoxide ring with Red-Al[23] gave the targeted segment with the anti, syn, anti stereochemistry. Paterson’s approach to the synthesis of this segment is shown in Scheme 6.[24] The (R)-Roche ester–derived ethyl ketone was first converted to the (E)–boron enolate with dicyclohexylboron chloride and an aldol reaction with the long-chain ynoate aldehyde gave the desired anti, anti aldol adduct in 96% yield with ≥97% ds. The stereochemistry at C9 was set through an Evans–Tishchenko reduction.
In connection with a project aimed at a total synthesis of calyculin, we investigated a boron enolate–mediated aldol reaction followed by Narasaka–Pai stereodirected reduction[25] to construct a polypropionate segment C10–C13 with an anti, anti, anti stereochemistry. In the event, the product turned out to have the syn, anti, anti stereochemistry.[26] This unanticipated stereochemical result can be rationalized by the boxed model shown in Scheme 7. Though not conducive to our original synthetic plan, this prompted us to endeavor toward the synthesis of another natural product, amphotericin B. Amphotericin B (AmB), produced by Streptomyces nodosus,[27] is one of the most prominent members of the clinically important polyene macrolides.[28] It is widely used as an antifungal agent, and serves as the drug of choice in the clinic for antifungal chemotherapy in life-threatening infections.[29] The C33–C37 fragment of amphotericin B (boxed in Figure 5) is a tripropionate segment containing four contiguous stereocenters with type 4 syn, anti, anti stereochemistry. Our own synthesis of the C33–C37 fragment of AmB commenced with a chiral orthoester derived from l-tartrate which reacted with the silyl enol ether of thiopyranone to give a chiral formylthiopyranone equivalent (Scheme 8).[30] Its silyl enol ether reacted with acetaldehyde in a titanium-catalyzed Mukaiyama aldol reaction to furnish the fragment with three
Fig. 5. Type 4 stereotetrad with syn, anti, anti stereochemistry: amphotericin B.
Fig. 6. Type 6 stereotetrad with syn, anti, syn stereochemistry: pironetin.
Scheme 8. Koskinen synthesis of the amphotericin B C33–C37 fragment.
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stereocenters correctly set. Final steps included a stereodirected reduction of the hydroxyketone to set the final stereocenter, and reductive desulfurization with Raney nickel. The synthesis of the C33–C37 fragment involves only six steps from l-tartrate and scales up readily. Type 6—syn, anti, syn Pironetin or PA-48153C is an unsaturated δ-lactone derivative isolated from Streptomyces species.[31] It possesses plant growth regulatory properties as well as immunosuppressive activity, which is manifested through a pathway different from the established immunosuppressants cyclosporin A and FK506. Pironetin contains a type 6 syn, anti, syn stereotetrad at C7–C10 (boxed in Figure 6). The innate syn aldol selectivity of the (Z)–dibutylboron enolate was again utilized twice in the synthesis of the pironetin syn, anti, syn fragment by Dias (Scheme 9).[32] Thus, the dibutylboron enolate of the (S)-oxazolidinone was first reacted with the hydroxypropionaldehyde derivative to set the C9 and C10 stereochemistries. After conversion of the
oxazolidinoyl chiral auxiliary to an aldehyde function through the Weinreb amide, a second Evans aldol reaction with the (R)-oxazolidinone–derived dibutylboron enolate gave the C7 and C8 stereocenters in a syn fashion. The 8,9-anti relationship was gained in >95:5 diastereoselectivity, testifying to the efficient reagent control by the Evans chiral auxiliary to override Felkin selectivity in the addition step. Type 7—anti, syn, syn Immunosuppressing agents have received enormous attention during the past two decades, and novel modes of action have enabled the investigation of several new structural classes of natural products exhibiting immunosuppressive activity. Stevastelins (Figure 7), one such novel group, were originally isolated from culture broths of Penicillium sp. NK374186.[33] Stevastelins are depsipeptides which contain a substituted stearic acid subunit incorporating a type 7 anti, syn, syn stereotetrad propionate unit. Sarabia et al. began the synthesis of the stereotetrad of stevastelins with the Evans aldol methodology to create the first
Scheme 9. Dias synthesis of the C6–C12 segment of pironetin.
Fig. 7. Type 7 stereotetrad with anti, syn, syn stereochemistry: stevastelins.
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two stereocenters in a syn manner (Scheme 10).[34] The other two stereocenters were created via a second aldol reaction of the (E)–boron enolate of t-butyl thiopropionate and the chiral aldehyde. Only one diastereomer, the desired anti, syn, syn product was obtained, following Felkin–Anh selectivity. Type 8—syn, syn, syn Erythromycins and erythronolides (Figure 8) and their derivatives are among the earliest and by far the most extensively studied macrolide antibiotics (more than 50 000 references at the time of writing this review). Erythromycin A was isolated in the early 1950s from a strain of Saccharopolyspora erythraea (Streptomyces erythraeus),[35] and its complete structure was revealed in 1965 by X-ray analysis. The antibiotic activity of erythromycins is related to their ability to inhibit ribosomaldependent protein biosynthesis.[36]
The structure of erythromycin was deemed “hopelessly complex, particularly in view of its plethora of asymmetric centers,”[37] and for over four decades the challenging structures of erythromycins and erythronolides attracted many research groups, but surprisingly few total syntheses have been reported.[38] The C2–C5 fragment of erythromycins contains a type 8 all-syn stereotetrad (boxed in Figure 8). A total synthesis of erythromycins published in 2003 by Martin et al. (Scheme 11)[39] involved the synthesis of the syn, syn, syn stereotetrad fragment. The synthesis started with an Evans aldol reaction of a (Z)–boron enolate to give the syn aldol adduct as the only isomer. After several reaction steps, which concentrated on the synthesis of the left half of erythromycin B, two missing stereocenters of the syn, syn, syn stereotetrad were created via asymmetric crotylation.
3. Conclusions Figure 9 shows a summary of the polyketide types synthesized and discussed in this text. The versatility of the Mukaiyama
Scheme 10. Sarabia synthesis of a stevastelin segment.
Fig. 8. Type 8 stereotetrad with syn, syn, syn stereochemistry: erythromycin B.
Scheme 11. Martin synthesis of the erythromycin B stereotetrad C2–C5.
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Fig. 9. Stereotetrad types synthesized using the boron enolate aldol reaction.
boron-mediated aldol reaction is evident: all structural classes, except type 5, have been synthesized with this methodology. Type 5 represents an exception, and deserves a comment that points out an interesting feature in the overall scenario. It turns out that this stereotetrad type is very rare in nature, occurring in only a few natural products.[40] No syntheses involving the aldol strategy have been reported so far. The boron enolate aldol strategy has proven its versatility in the syntheses of polyketide stereotetrads, and the outlook for further developments is promising. New developments for more elaborate structures, catalytic enolization methods and asymmetric induction protocols will undoubtedly broaden the scope of this powerful technology even further.
[8]
[9] [10] [11] [12]
[13] [14]
REFERENCES [1] [2]
[3]
[4] [5] [6] [7]
a) R. Kane, Ann. Phys. 1838, 120, 473–494; b) R. Kane, J. Prakt. Chem. 1838, 15, 129–155. a) A. Borodin, J. Prakt. Chem. 1864, 93, 413–425; b) A. Wurtz, Bull. Soc. Chim. Fr. 1872, 17, 436–442; c) A. Wurtz, J. Prakt. Chem. 1872, 5, 457–464; d) A. Wurtz, C. R. Hebd. Seances Acad. Sci. 1872, 74, 1361–1367; e) A. Wurtz, Chem. Ber. 1872, 5, 326–327. For leading general reviews on the aldol reaction, see e.g., a) A. T. Nielsen, W. T. Houlihan, Org. React. 1968, 16, 1–438; b) T. Mukaiyama, Org. React. 1982, 28, 203–331; c) B. Schetter, R. Mahrwald, Angew. Chem., Int. Ed. 2006, 45, 7506–7525; d) E. M. Carreira, A. Fettes, C. Marti, Org. React. 2006, 67, 1–216. J. Matsuo, M. Murakami, Angew. Chem., Int. Ed. 2013, 52, 9109–9118. T. Mukaiyama, T. Inoue, Chem. Lett. 1976, 5, 559–562. T. Mukaiyama, K. Inomata, Bull. Chem. Soc. Jpn. 1971, 44, 3215. For reviews, see: a) C. J. Cowden, I. Paterson, Org. React. 1997, 51, 1–200; b) T. Mukaiyama, J.-I. Matsuo, in Modern Aldol
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[15] [16] [17] [18]
[19] [20]
[21] [22]
Chem. Rec. 2014, 14, 52–61
Reactions (Ed.: R. Mahrwald), Wiley-VCH, Weinheim, Germany, 2008. J. B. Hendrickson, The Molecules of Nature: A Survey of the Biosynthesis and Chemistry of Natural Products, BenjaminCummings Publishing Company, Reading, Massachusetts, 1965, p. 33. For a recent review on polyketide biosynthesis, see C. Hertweck, Angew. Chem., Int. Ed. 2009, 48, 4688–4716. W.-C. Liu, D. Smith-Slusarchyk, G. Astle, W. H. Trejo, W. E. Brown, E. Meyers, J. Antibiot. 1978, 31, 815–819. D. A. Evans, R. L. Dow, T. L. Shih, J. M. Takacs, R. Zahler, J. Am. Chem. Soc. 1990, 112, 5290–5313. A. I. Meyers, K. A. Babiak, A. L. Campbell, D. L. Comins, M. P. Fleming, R. Henning, M. Heuschmann, J. P. Hudspeth, J. M. Kane, P. J. Reider, D. M. Roland, K. Shimizu, K. Tomioka, R. D. Walkup, J. Am. Chem. Soc. 1983, 105, 5015–5024. D. A. Evans, E. B. Sjogren, J. Bartroli, R. L. Dow, Tetrahedron Lett. 1986, 27, 4957–4960. K. Yamada, M. Ojika, H. Kigoshi, K. Suenaga, Nat. Prod. Rep. 2009, 26, 27–43. K. Yamada, M. Ojika, T. Ishigaki, Y. Yoshida, H. Ekimoto, M. Arakawa, J. Am. Chem. Soc. 1993, 115, 11020–11021. For a review on actin-binding macrolides, see: K. S. Yeung, I. Paterson, Angew. Chem., Int. Ed. 2002, 41, 4632–4653. I. Paterson, S. B. Blakey, C. J. Cowden, Tetrahedron Lett. 2002, 43, 6005–6008. a) T. Mukaiyama, R. W. Stevens, N. Iwasawa, Chem. Lett. 1982, 11, 353—356; b) T. Mukaiyama, N. Iwasawa, Chem. Lett. 1982, 11, 1903–1906. D. A. Evans, A. H. Hoveyda, J. Am. Chem. Soc. 1990, 112, 6447–6449. a) H. Kigoshi, M. Ojika, T. Ishigaki, K. Suenaga, T. Mutou, A. Sakakura, T. Ogawa, K. Yamada, J. Am. Chem. Soc. 1994, 116, 1443–1444; b) H. Kigoshi, K. Suenaga, T. Mutou, T. Ishigaki, T. Atsumi, H. Ishiwata, A. Sakakura, T. Ogawa, M. Ojika, K. Yamada, J. Org. Chem. 1996, 61, 5326–5351. D. A. Evans, J. Bartroli, T. L. Shih, J. Am. Chem. Soc. 1981, 103, 2127–2129. T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974–5976.
© 2014 The Chemical Society of Japan and Wiley-VCH, Weinheim
B o ro n En o l a t e s i n Po l y k e t i d e St e re o t e t r a d Sy n t h e s i s
[23]
[24] [25] [26] [27] [28] [29] [30] [31]
[32] [33]
a) J. M. Finan, Y. Kishi, Tetrahedron Lett. 1982, 23, 2719– 2722; b) K. C. Nicolaou, J. Uenishi, J. Chem. Soc., Chem. Commun. 1982, 1292–1293. I. Paterson, C. J. Cowden, M. D. Woodrow, Tetrahedron Lett. 1998, 39, 6037–6040. K. Narasaka, F. C. Pai, Chem. Lett. 1980, 9, 1415–1418. K. Karisalmi, A. M. P. Koskinen, Synthesis 2004, 1331–1342. H. A. B. Linke, W. Mechlinski, C. P. Schaffner, J. Antibiot. 1974, 27, 155–160. Macrolide Antibiotics: Chemistry, Biology and Practice (Ed.: S. Omura), Academic Press, New York, 1984. P. A. Hunter, Drug Discovery Today 1996, 1, 227–228. K. Karisalmi, K. Rissanen, A. M. P. Koskinen, Org. Biomol. Chem. 2003, 1, 3193–3196. a) S. Kobayashi, K. Tsuchiya, T. Harada, M. Nishide, T. Kurokawa, T. Nakagawa, N. Shimada, K. Kobayashi, J. Antibiot. 1994, 47, 697–702; b) S. Kobayashi, K. Tsuchiya, T. Kurokawa, T. Nakagawa, N. Shimada, Y. Iitaka, J. Antibiot. 1994, 47, 703–707; c) T. Yoshida, K. Koizumi, Y. Kawamura, K. Matsumoto, H. Itazaki, Eur. Pat. Appl. 560389 A1, 1993; d) K. Yasui, Y. Tamura, T. Nakatani, K. Kawada, M. Ohtani, J. Org. Chem. 1995, 60, 7567–7674. L. C. Dias, L. G. Oliveira, M. A. de Sousa, Org. Lett. 2003, 5, 265–268. a) T. Morino, A. Masuda, M. Yamada, M. Nishimoto, T. Nishikori, S. Saito, N. Shimada, J. Antibiot. 1994, 47, 1341– 1343; b) T. Morino, K.-I. Shimada, A. Masuda, M. Nishimoto, S. Saito, J. Antibiot. 1996, 49, 1049–1051.
Chem. Rec. 2014, 14, 52–61
[34] [35]
[36] [37] [38] [39]
[40]
F. Sarabia, S. Chammaa, F. J. López-Herrera, Tetrahedron Lett. 2002, 43, 2961–2965. J. M. McGuire, R. L. Bunch, R. C. Anderson, H. E. Boaz, E. H. Flynn, H. M. Powell, J. W. Smith, Antibiot. Chemother. (Washington, D. C.) 1952, 2, 281–283. a) S. Pal, Tetrahedron 2006, 62, 3171–3200; b) B. Vester, S. Douthwaite, Antimicrob. Agents Chemother. 2001, 45, 1–12. R. B. Woodward in Perspectives in Organic Chemistry (Ed.: A. R. Todd), Interscience, New York, 1956, p. 160. For a review, see: X. Gao, S. K. Woo, M. J. Krische, J. Am. Chem. Soc. 2013, 135, 4223−4226. a) S. F. Martin, W.-C. Lee, G. J. Pacofsky, R. P. Gist, T. A. Mulhern, J. Am. Chem. Soc. 1994, 116, 4674–4688; b) P. J. Hergenrother, A. Hodgson, A. S. Judd, W.-C. Lee, S. F. Martin, Angew. Chem., Int. Ed. 2003, 42, 3278–3281; c) P. Breton, P. J. Hergenrother, T. Hida, A. Hodgson, A. S. Judd, E. Kraynack, P. R. Kym, W.-C. Lee, M. S. Loft, M. Yamashita, S. F. Martin, Tetrahedron 2007, 63, 5709–5729. Lankamycin and lankacidin: a) E. Gaumann, R. Hutter, W. Keller-Schierlein, L. Neipp, V. Prelog, H. Zahner, Helv. Chim. Acta 1960, 43, 601–606. Portmicin: b) R. L. Hamill, R. C. Yao, U.S. Patent 4,582,822, 1986; c) Y. Kusakabe, N. Takahashi, Y. Iwagaya, A. Seino, J. Antibiot. 1987, 40, 237–238. Enteridinine: d) T. Rezanka, R. Dvorˇáková, L. O. Hanuš, V. M. Dembitsky, Phytochemistry 2004, 65, 455–462. Langkolide: e) S. E. Helaly, A. Kulik, H. Zinecker, K. Ramachandaran, G. Y. A. Tan, J. F. Imhoff, R. D. Suessmuth, H.-P. Fiedler, V. Sabaratnam, J. Nat. Prod. 2012, 75, 1018–1024.
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