Patent ID: 6172205
Filing Date: 2001-01-09
Classification: C07H

Abstract:
A process for the preparation of an Eleutherobin analogue of the formula: ##STR70##whereinR.sub.1 is a hydrogen, ester, nitrile, trifolate or CH.sub.2 -R.sub.4 wherein;R.sub.4 is a carbohydrate, an alcohol, an amine, an amide, an alkyne,or C.sub.1 -C.sub.9 linear or branched chain alkyl;R.sub.2 is a linear or branched alkyl moiety;R.sub.3 is an ester, an amide, a carbamate, an acetal compound, an ether or a urethane;position C.sub.2 and C.sub.3 is cis or trans;position C.sub.8 is .alpha. or .beta.,comprising the steps of:(a) treating a chiral matrix material with a ketene under suitable conditions to form a compound having the structure: ##STR71##wherein X is a halogen; and(b) dehalogenating the compound in step (a) under suitable conditions to form a compound having the structure: ##STR72##(c) subjecting the compound in step (b) to a Bredereck transformation to form a compound having the structure: ##STR73##(d) acid catalyzing and fragmenting the compound in step (c) under suitable conditions to form a compound having the structure: ##STR74##(e) appending a furanoid building block to the compound formed in step (d) under suitable conditions to form a compound having the structure: ##STR75##wherein X is .alpha.-OH, .beta.-H or .alpha.-H, .beta.-OH,(f) protecting the compound formed in step (e) under suitable conditions to form a compound having the structure: ##STR76##wherein X is .alpha.-OTBDPS, .beta.-H or .alpha.-H, .beta.-OTBDPS; and(g) expanding the compound in step (f) under suitable conditions to form a compound having the structure: ##STR77##(h) performing a Nozaki-Kishi reaction on the compound in step (g) to form a compound having the structure: ##STR78##(i) protecting the compound formed in step (h) under suitable conditions to form a compound having the structure: ##STR79##(j) treating the compound in step (i) under conditions suitable to the removal of OTBDPS to form a compound having the structure: ##STR80##(k) treating the compound in step (j) with dimethyldioxirane under suitable conditions to form a compound having the structure: ##STR81##(l) protecting the compound in step (k) under suitable conditions to form a compound having the structure: ##STR82##(m) methylating the compound in step (k) or (l) under suitable conditions to form a compound having the structure: ##STR83##(n) treating compound (2) in step (m) with acetic anhydride under suitable conditions to form a compound having the structure: ##STR84##(o) acid catalyzing compound (1) in step (m) under suitable conditions to form a compound having the structure: ##STR85##whereinR is a linear or branched chain alkyl group;(p) protecting, deprotecting and converting the compound in step (o) under suitable conditions to form a compound having the structure: ##STR86##whereinR is a linear or branched chain alkyl group and P is a protecting group;(q) treating the compound in step (p) under suitable conditions to form a compound having the structure: ##STR87##