Convenient Synthesis of Two Mango Allergens

Shyam V. Trivedi, Ayyulur S. Subbaraman, Subrata Chattopadhyay and Vasant R.Mamdapur*Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai – 400 085, India 57007Tel.: (022)-550-5050, Fax: (022) 550-5151, E-mail: schatt@apsara.barc.in* Author to whom correspondence should be addressed.Received: 10 September 1998 / Accepted: 16 July 1999 / Published: 30 August 1999Abstract: The mango allergens, 5[2’(Z)-heptadecenyl]resorcinol (10) and 5[12’(Z)-heptadecenyl]resorcinol (20) have been synthesized by simple routes using easily accessiblestarting materials.Keywords: Mango allergens, synthesis, phenolics.IntroductionIt is by now established [1] that several long chain phenolic compounds act as natural allergensimparting resistant properties to plants. Amongst the various sources of the allergens, the cashew nutshell as well as the Japanese and Chinese lacs are well known for producing the phenolic compoundslike cardols [2] and urushiols [3]. Sometimes back, we have isolated [4] a non-volatile allergen,5[2’(Z)-heptadecenyl]resorcinol (10) from the mango latex. Subsequently, another isomeric resorcinolviz. 5[12’(Z)-heptadecenyl]resorcinol (20) was isolated by Cojocaru et al. [5] from raw mango fruitpeel. They have demonstrated that these phenolic compounds also act as preservatives in the necroticorgans of the plants against microbial infection. Considering that occupational allergenic contactdermatitis is a growing problem in the green house industry, the study of mango allergen seemsinteresting. With this aim, we have developed a novel synthesis of the above compounds in sufficientquantities to study their allergen and other biological activities. The synthesis (Scheme 1) is brief andconveniently produces the target compounds from easily accessible starting materials.


Introduction
It is by now established [1] that several long chain phenolic compounds act as natural allergens imparting resistant properties to plants.Amongst the various sources of the allergens, the cashew nut shell as well as the Japanese and Chinese lacs are well known for producing the phenolic compounds like cardols [2] and urushiols [3].Sometimes back, we have isolated [4] a non-volatile allergen, 5[2'(Z)-heptadecenyl]resorcinol (10) from the mango latex.Subsequently, another isomeric resorcinol viz.5[12'(Z)-heptadecenyl]resorcinol (20) was isolated by Cojocaru et al. [5] from raw mango fruit peel.They have demonstrated that these phenolic compounds also act as preservatives in the necrotic organs of the plants against microbial infection.Considering that occupational allergenic contact dermatitis is a growing problem in the green house industry, the study of mango allergen seems interesting.With this aim, we have developed a novel synthesis of the above compounds in sufficient quantities to study their allergen and other biological activities.The synthesis (Scheme 1) is brief and conveniently produces the target compounds from easily accessible starting materials.

Synthesis of 5[2'(Z)-heptadecenyl]resorcinol (10)
Commercially available 1-tetradecanol (1) was converted to the bromide 2 via a standard route and reacted with monosodium acetylide [6] to furnish the alkyne 3.For the required aromatic moiety, 3,5dihydroxybenzoic acid (4) was converted to the ester 5 by esterification followed by methylation.Its LAH reduction to the alcohol 6 followed by chlorination gave compound 7. Alkylation [7] of the alkyne 3 with the chloride 7 was accomplished using n-BuLi as the base in the presence of CuI to furnish 8. Its cis-selective partial hydrogenation afforded the dimethyl ether 9 which was demethylated with BBr 3 to furnish the target allergen 10.
In an alternative approach, 10-undecenol (21) was brominated to give 22.As above, the Grignard reagent prepared from 22 was reacted with 3,5-dimethoxybenzaldehyde to furnish the alcohol 23 which on mesylation and LAH reduction afforded the alkene 24.This on anti-Markonikov hydration with NaBH 4 -TiCl 4 [11] followed by pyridinium chlorochromate (PCC) [12] oxidation gave the aldehyde 26.Its Z-selective Wittig olefination with n-pentyltriphenylphosphonium bromide in the presence of dimsyl ion as the base led to 19.As done for 10, demethylation of 19 with BBr 3 afforded the title compound 20.The spectral and microanalytical data of both the synthetic samples were in good agreement with those reported [4,5] in literature.

General
All the boiling points are uncorrected.The IR spectra were scanned with a Perkin-Elmer spectrophotometer model 837.The PMR spectra were recorded in CDCl 3 with a Varian A-60 (60 MHz) instrument.The GLC analyses were carried out using Shimadzu GC-7A chromatograph using a 3% OV-17 column and a N 2 flow rate 40 mL/min.Anhydrous reactions were carried out under Ar using freshly dried solvents.The organic extracts were dried over anhydrous Na 2 SO 4 .

5-(12'(Z)-Heptadecenyl)-resorcinol dimethyl ether (19)
To a cooled (0 0 C) and stirred solution of 18 (3.9g, 0.01 mol) and TEA (2.1 mL, 0.012 mol) in CH 2 Cl 2 (30 mL) was added mesyl chloride (1.1 mL, 0.012 mol).The mixture was stirred at the same temperature for 3 h, poured in ice-water, the organic layer separated and the aqueous portion extracted with CHCl 3 .The combined organic extract was washed with water and brine, dried and concentrated in vacuo to get a residue which was used directly for the next step.

5-(12'(Z)-Heptadecenyl)-resorcinol dimethylether (19)
To a stirred solution of dimsyl ion [0.012 mol, in DMSO (30 mL)] was added npentyltriphenylphosphonium bromide (5.0 g, 0.012 mol) in portions.After stirring for 1 h, the resulting red ylide was diluted with THF (40 mL), cooled to -20 0 C and the aldehyde 26 (3.2 g, 0.01 mol) in THF (10 mL) added in dropwise manner.Stirring was continued for 1 h at the same temperature and at room temperature for 12 h.Water was added to the mixture, the organic layer separated and the aqueous portion extracted with ether.The organic extract was washed with water and brine, dried, concentrated and the residue purified as earlier to get pure 19.Its spectral data were identical with those of the product obtained by the other route.yield:1.8g (48%).