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Enantioselective Entry to the Homalium Alkaloid Hoprominol: Synthesis of an ( R , R , R )‐Hoprominol Derivative
Author(s) -
Ensch Corinne,
Hesse Manfred
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390016
Subject(s) - chemistry , enantioselective synthesis , derivative (finance) , conjugate , stereochemistry , alkylation , intramolecular force , bicyclic molecule , amination , total synthesis , michael reaction , organic chemistry , catalysis , mathematical analysis , mathematics , financial economics , economics
The diastereoselective synthesis of the N ‐ and O ‐protected hoprominol derivative ( R , R , R )‐ 6 is described. The building up of the bicyclic O ‐silylated and di( N ‐tosylated) asymmetric scaffold 6 succeeded by convergent preparation of the two basic chiral azalactam units 7a and 7b and their subsequent iterative linking by a known method ( Scheme 5 ). Both 4‐alkyl‐hexahydro‐1,5‐diazocin‐2(1 H )‐ones 7a and 7b were prepared from the chiral β ‐amino acid portions 10a and 10b , respectively, by application of a set of reactions ( e.g., N ‐alkylation of 10a , b and Sb(OEt) 3 ‐assisted cyclization of the resulting open‐chain intermediates) already known. In comparison with the total syntheses of homaline ( 1 ) and homoprine ( 2 ), the newness of the described synthesis lies in the asymmetric approach to the difunctionalized fatty acid derivative 10b starting from (−)‐( S )‐malic acid ( 9 ) ( Schemes 3 and 4 ). Key step in the preparation of 10b was the diastereoselective amination of the optically pure α , β ‐unsaturated δ ‐hydroxy homoallylic ester 14 via conjugate intramolecular aza‐ Michael cyclization of the acylic δ ‐(carbamoyloxy) intermediate 11 .