Journal o f Chemical Ecology, Vol. 8, No. 4, 1982
NEW SYNTHESIS OF ROYAL JELLY ACID
ROBERT CHIRON Laboratoire de Chimie Organique-U.E.R. de Chimie B.P. 1044-44072 Nantes Cedex, France
(Received October 31, 1980; revised August 2, 1981) Abstraet--A new synthesis of (E)-I 0-hydroxy-2-decenoic acid (royal jelly acid) is described, starting from 8-bromo-l-octanol via condensation of malonic acid with 8-hydroxyoctanal or 8-acetoxyoctanal. Key Words--Royal jelly acid, (E)-10-hydroxy-2-decenoic acid, honeybee, Apis mellifera, Hymenoptera, Apidae
INTRODUCTION
Ten-carbon aliphatic compounds are prominent among those isolated from the honeybee Apis mellifera (L.). In particular, the royal jelly, secreted by the mandibular glands of worker bees, contains an important amount of (E)-10hydroxy-2-decenoic acid (A) (Royal Jelly Acid). HO--(CH2)7--CH~-~-CH--COOH
A
This acid is interesting because of its relationship to queen pheromone: 9-oxo and (E)-9-hydroxy-2-decenoic acid. Pain et al. (1974) have shown that parallels exist between the yearly cycle of the acid and the secretions of the queen pheromones, which are responsible for the attraction of young honeybees, and the inhibition of their ovaries and ability to produce queen cells. Since 1960, many syntheses for this acid alcohol have been proposed, condensation of various aldehydes with malonic acid being frequently used (Fray, 1960; Fusii, 1960; Sisido, 1962; Smissman, 1964; Fournet, 1965; Bestmann, 1966). We have found two new methods which give a faster synthesis and higher yields; these start with 8-bromo-l-octanol and use as intermediates three aldehydes obtained by the oxidation of a -CH2Br group by pyridine oxide. 709 0098-0331/8210400-0709503.00/09 1982Plenum PublishingCorporation
710
CmRON
These three aldehydes, 8-hydroxyoctanal, its tetrahydropyranyl (THP) derivative, and 8-acetoxyoctanal then undergo malonic synthesis, and by decarboxylation, the acid is obtained.
METHODS AND MATERIALS Infrared data were obtained with a Beckman IR-18 A instrument; nuclear magnetic resonance data were obtained with a Varian A-60 instrument. The reaction schemes are shown in Figures 1 and 2. 8-Bromo-l-octanol 1 A solution of 1,8-octanediol in petroleum ether (bp 50-70 ~ was refluxed with 35% HBr aqueous solution, under continuous extraction during 15 hr. Fractional distillation yielded 75% of the bromo derivative; bp 92 ~ ram. 8-Hydroxyoctanal THP Ether 3 The T H P ether of 8-bromo-l-octanol (29.3 g, 0.1 tool) was added to a suspension of pyridine-N-oxide (19 g, 0.2 tool) and NaHCO3 (22 g, 0.25 tool) in 180 ml of anhydrous toluene. The mixture was stirred overnight under reflux, and water was added (500 ml). After extraction with benzene and drying (MgSO4), the solvents were removed, and distillation yielded 12 g, bp 128~ mm (70%) of the aldehyde 3; IR, 1730 (CO) cm -1.
- (CH2) 8Br i
- (CH2)7-CHO
2
~ o -
3_
(CH 2) 7CH=C~-COO~
S
HO-(CH2)7-CH=CH-COOH A HO- (CH25)7-CHO ~
-
(CH
H-OH
NEW SYNTHESIS OF ROYAL JELLY ACID
ROBERT CHIRON Laboratoire de Chimie Organique-U.E.R. de Chimie B.P. 1044-44072 Nantes Cedex, France
(Received October 31, 1980; revised August 2, 1981) Abstraet--A new synthesis of (E)-I 0-hydroxy-2-decenoic acid (royal jelly acid) is described, starting from 8-bromo-l-octanol via condensation of malonic acid with 8-hydroxyoctanal or 8-acetoxyoctanal. Key Words--Royal jelly acid, (E)-10-hydroxy-2-decenoic acid, honeybee, Apis mellifera, Hymenoptera, Apidae
INTRODUCTION
Ten-carbon aliphatic compounds are prominent among those isolated from the honeybee Apis mellifera (L.). In particular, the royal jelly, secreted by the mandibular glands of worker bees, contains an important amount of (E)-10hydroxy-2-decenoic acid (A) (Royal Jelly Acid). HO--(CH2)7--CH~-~-CH--COOH
A
This acid is interesting because of its relationship to queen pheromone: 9-oxo and (E)-9-hydroxy-2-decenoic acid. Pain et al. (1974) have shown that parallels exist between the yearly cycle of the acid and the secretions of the queen pheromones, which are responsible for the attraction of young honeybees, and the inhibition of their ovaries and ability to produce queen cells. Since 1960, many syntheses for this acid alcohol have been proposed, condensation of various aldehydes with malonic acid being frequently used (Fray, 1960; Fusii, 1960; Sisido, 1962; Smissman, 1964; Fournet, 1965; Bestmann, 1966). We have found two new methods which give a faster synthesis and higher yields; these start with 8-bromo-l-octanol and use as intermediates three aldehydes obtained by the oxidation of a -CH2Br group by pyridine oxide. 709 0098-0331/8210400-0709503.00/09 1982Plenum PublishingCorporation
710
CmRON
These three aldehydes, 8-hydroxyoctanal, its tetrahydropyranyl (THP) derivative, and 8-acetoxyoctanal then undergo malonic synthesis, and by decarboxylation, the acid is obtained.
METHODS AND MATERIALS Infrared data were obtained with a Beckman IR-18 A instrument; nuclear magnetic resonance data were obtained with a Varian A-60 instrument. The reaction schemes are shown in Figures 1 and 2. 8-Bromo-l-octanol 1 A solution of 1,8-octanediol in petroleum ether (bp 50-70 ~ was refluxed with 35% HBr aqueous solution, under continuous extraction during 15 hr. Fractional distillation yielded 75% of the bromo derivative; bp 92 ~ ram. 8-Hydroxyoctanal THP Ether 3 The T H P ether of 8-bromo-l-octanol (29.3 g, 0.1 tool) was added to a suspension of pyridine-N-oxide (19 g, 0.2 tool) and NaHCO3 (22 g, 0.25 tool) in 180 ml of anhydrous toluene. The mixture was stirred overnight under reflux, and water was added (500 ml). After extraction with benzene and drying (MgSO4), the solvents were removed, and distillation yielded 12 g, bp 128~ mm (70%) of the aldehyde 3; IR, 1730 (CO) cm -1.
- (CH2) 8Br i
- (CH2)7-CHO
2
~ o -
3_
(CH 2) 7CH=C~-COO~
S
HO-(CH2)7-CH=CH-COOH A HO- (CH25)7-CHO ~
-
(CH
H-OH
