Antheridic acid

Retrosynthetic analysis of antheridic acid produced a totally different plan of synthesis from that which had been employed for the structurally related target gibberellic acid. The synthesis of antheridic acid, which included a number of novel steps, allowed definitive assignment of structure and revised stereochemistry at C(3). 

Compound A possesses the structure originally proposed for the methyl ester of Aao (see K. Nakanishi, M. Endo, U. Naf, and L. F. Johnson, J. Am. Chem. Soc, 1971, 93, 5579). However, the 270-MHz NMR spectrum of synthetic A was different from that reported for Aah methyl ester with respect to the protons at C(3) and C(5). Therefore, the 3a-alcohol, compound B, was synthesized as shown below. 

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Intramolecular cyclopropanation using diazoesters is a powerful synthetic tool. Diazoesters are readily prepared from the corresponding alcohol via House s methods56-57. Numerous examples using the application of this transformation in synthesis have been reported. These include the potent synthetic pyrethroid NRDC 182 (22)58, (1 R)-( )-cis-chrysanthemic acid (23)59, the highly strained bicyclic system 2460, antheridic acid 2561,62 and cycloheptadiene 26 (equations 33-37). 

The method has also recently been used in a short synthesis of lipoic acid (Scheme and featured in MacMillan s conversion (equation 12a) of gibberellin As (23) into gibberellins As (24) and Ass (25), and in Mander s conversion of gibberellin A (26) into antheridic acid (equation 12b). In these last two examples the terminally disubstituted alkenes were oxidized widi almost complete stereoselectivity to give the IS-hydroxy pr ucts consistent widi sterically controlled tqrproach of the reagent The trisub-stituted double bond in equation (12b) was unaffected, as was the remaining fimctionidity in bodi substrate molecules. 

The enantioseiective total synthesis of antheridic acid involves the key O-heterocyclic intermediate 375 produced by an intramolecular addition... 

The enantioselective total synthesis of (+)-antheridic acid was accomplished by E.J. Corey and co-workers using the Lewis-acid-mediated vinyicyciopropane-cyciopentene rearrangement as the key step. This key transformation was not possible under thermal conditions however, the use of excess diethylaluminum chloride in DCM gave rise to the rearranged product in excellent yield. 

Corey, E. J., Kigoshi, H. A route for the enantioselective total synthesis of antheridic acid, the antheridium-inducing factor from Anemia phyllitidis. Tetrahedron Lett. 1991, 32, 5025-5028. 

Scheme 11.33 Corey s synthesis of (+)-antheridic acid involving the Et2AlCl-promoted rearrangement of highly functionalized VCP 41.

Antheridic acid, A-60278 Asadanol, in A-60308 5-Formylzearalenone, in Z-60002 Isotaxiresinol, 1-60139 l(10)-Millerenolide, M-60136 9-Millerenolide, M-60137 Strigol, S-60057... 

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