CHIROSPECIFIC SYNTHESES OF NITROGEN AND SIDE-CHAIN MODIFIED ANATOXIN ANALOGS - SYNTHESIS OF (1R)-ANATOXINAL AND (1R)-ANATOXINIC ACID-DERIVATIVES

A straightforward and good yielding route to side-chain analogues of the potent neurotoxin and neurotransmitter (+)-anatoxin (1) has been developed. Peroxy acid oxidation of the (silyloxy)butadiene 43 derived from readily synthesized, optically pure (Ifl)-t-BOC-anatoxin (42) affords silyloxy ketone 44. Fluorolysis of 44 followed by oxidative cleavage of the resultant α-hydroxy ketone 45 gives a mixture of αβ-unsaturated acid 46 and ester 41 in 57% combined yield. Other approaches to these compounds, based on literature precedent, failed. (lfl)-i-BOC-anatoxinic acid (46) then serves as educt for the synthesis of a wide variety of anatoxin derivatives with modified side-chain functionality. These analogues, designed to serve as probes of the agonist binding site of the nicotinic acetylcholine receptor, include alcohol, aldehyde, amide, hydroxamate, and oxime ether functional groups. © 1990, American Chemical Society. All rights reserved.