Patent ID: 6051721
Filing Date: 2000-04-18
Classification: C07D,C07H

Abstract:
A process for preparing an enantiomerically enriched compound corresponding to the formula (I) or (II): ##STR36## wherein R is: ##STR37## and X, X', Y, Y' and Z may each be hydrogen; deuterium; tritium; a C.sub.1 -C.sub.8 saturated or unsaturated, alkyl or cycloalkyl group; a hydroxyl group; an ether-protected hydroxyl group bearing a C.sub.1 -C.sub.8 saturated or unsaturated alkyl or cyclic alkyl group; a carboxylate ester-protected hydroxyl group derived from a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, carboxylic acid; a hydroxyl group protected as a phosphate mono-, di- or triester, the di-, or triester having C.sub.1 -C.sub.4 saturated or unsaturated alkyl group(s); a phosphonate mono- or diester-protected hydroxyl group derived from a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, phosphonic acid wherein the diester also contains a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group; a phosphinate ester-protected hydroxyl group derived from a phosphinic acid bearing two C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl groups; a hydroxyl group protected as a sulfate mono- or diester bearing a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group; a hydroxyl group protected as a sulfonate ester derived from a sulfonic acid bearing a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl group; an amino group; a primary or secondary amine bearing 1 to 2 C.sub.1 -C.sub.4 saturated or unsaturated alkyl group(s), respectively; a carboxamide-protected, unsubstituted or primary amino group bearing a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group and derived from a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, carboxylic acid; a carboxylic acid; a carboxylate ester bearing a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group; a phosphonic acid; a phosphonate mono- or diester bearing 1 to 2 C.sub.1 -C.sub.4 saturated or unsaturated alkyl group(s), respectively; a phosphinic acid having a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl group or ester bearing a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group; a formyl group; an acetyl group; a benzoyl group; a carboxamide group derived from ammonia, or a primary or secondary amine bearing 1 to 2 C.sub.1 -C.sub.4 saturated or unsaturated alkyl group(s), respectively; a sulfhydryl group; a thioether bearing a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl group; a sulfonic acid, a sulfonate ester bearing a C.sub.1 -C.sub.4 saturated or unsaturated alkyl group; an alkylsulfonyl group bearing a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl group; a phenylsulfonyl group; a sulfoxide bearing a C.sub.1 -C.sub.8 saturated or unsaturated, cyclic or acyclic, alkyl group; a phenylsulfoxide; a phenylseleno group; a phenylselenoxide; an azide; a halogen; a cyano group; a nitro group; a nitroso group; a diazonium group; or a trifluoromethyl group; and R.sup.1 is one ofa) --OH;b) an ether or glycoside;c) a substituted or unsubstituted amine or aniline;d) a C.sub.2 to C.sub.8 alkenyl group;e) a C.sub.1 to C.sub.8 alcohol;comprising subjecting a compound of formula (a); ##STR38## to silylation, deacetylation, and oxidation to produce a compound of formula (b) ##STR39## wherein R.sup.9 is a silyl protecting group; converting the compound of formula (b) to a compound of formula (c) by retro-Michael ring opening and protection of the C.sub.4 --OH followed by aldehyde oxidation ##STR40## wherein R.sup.10 is a C.sub.4 protecting group; converting the compound of formula (c) to a compound of formula (d) by transformation of the carboxylic acid into an acyl oxazolidinone functionality; ##STR41## converting the compound of formula (d) to a compound of formula (e) by Cu.sup.I -mediated conjugate addition of RMgBr at a temperature of -10 to 0.degree. C.; ##STR42## converting the compound of formula (e) to a compound of formula (f) by chemoselective silyl ether deprotection by heating with a fluoride source and cyclization to produce the corresponding lactone; ##STR43## converting the compound of formula (f) to a compound of formula (I) by generation and kinetic quenching of a C.sub.2 enolate and deprotection of the C.sub.4 OH.