Process for the preparation of D-(+)-biotin
AssigneeMerck Patent GmbH
InventorsEike Poetsch, Michael Casutt
Life of this patent
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Abstract
D-(+)-Biotin can be prepared from optically active hydantoins of the formula I ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, X and Y have the meaning given in patent claim 1, in a simple, stereospecific manner. Furthermore bicyclic nitriles of the formula XI ##STR2## wherein R.sup.1, R.sup.2, R.sup.3, X and Y have the meaning given represent precious intermediate products and educts of a multitude of possibilities to synthesize optically active D-(+)-biotin.
Claims18
A process for the preparation of D-(+)-biotin, comprising:
- (i) Reducing a starting material compound of the formula ##STR24## wherein R.sup.1 and R.sup.2 are each in independently H, alkyl, substituted alkyl, cycloalkyl, aryl, aralkyl or heteroaryl, wherein the heteroatom is O, N, or S, or taken together are alkylene, substituted alkylene or heteroalkylene, wherein the heteroatom is O, N, or S;
- R.sup.3 is H or benzyl, benzyl substituted by one or more of C.sub.1-4 -alkyl, C.sub.1-4 -alkoxyl, C.sub.35 alkyl-2-enyl or C.sub.3-6 -trialkylsilyl;
- X and Y independently are each O or S;
- to an alcohol of the formula ##STR25## by reacting said starting material compound with a reducing agent or by catalytically hydrogenating said starting material compound;
- (ii) converting said alcohol into an activated ester of the formula ##STR26## wherein R.sup.4 is an activating ester group and is alkanoyl, aroyl, alkylsulfonyl or azole.M, wherein azole is a fused or non-fused, substituted or unsubstituted, nitrogen-containing 5-membered ring, and M is CO, CS, SO.sub.2, SO or S;
- (iii) reacting said activated ester with an alkali metal cyanide, an alkaline earth metal cyanide or a cyanosilane, to give a nitrile of the formula ##STR27## (iv) reacting said nitrile with a base or an acid to give an acid derivative of the formula ##STR28## wherein R.sup.5 is H or alkyl;
- (v) cyclizing said derivative with water being split off, to give a lactone of the formula ##STR29## wherein R.sup.6 is H or R.sup.1 R.sup.2 CH;
- (vi) converting the product of step (v) by known processes to D-(+)-biotin.
In a process for the preparation of D-(+)-biotin, the improvement comprising reducing an intermediate compound of the formula ##STR31## wherein R.sup.1 and R.sup.2 are each independently H, alkyl, substituted alkyl, cycloakyl, aryl, aralkyl or heteroaryl, wherein the heteroatom is O, N, or S, or taken together are alkylene, substituted alkylene or heteroalkylene, wherein the heteroatom is O, N, or S;
- R.sup.3 is H or benzyl, benzyl substituted by one or more of C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, C.sub.3-5 -alk-2-enyl or C.sub.3-6 -trialkysilyl;
- X and Y independently are each O or S.
Dependencies are inferred from the claim text.