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Total Syntheses of the Spermine Alkaloids (−)‐( R , R )‐Hopromine and (±)‐Homaline
Author(s) -
Ensch Corinne,
Hesse Manfred
Publication year - 2002
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 - 10.1002/1522-2675(200206)85:6<1659::aid-hlca1659>3.0.co;2-d
Subject(s) - chemistry , stereochemistry , alkaloid , specific rotation , lactam , side chain , total synthesis , alkyl , natural product , spermine , organic chemistry , enzyme , polymer
The diastereoselective synthesis of the spermine alkaloid ( R , R )‐hopromine ( 2 ) is described. The as yet unknown absolute configuration of naturally occurring (−)‐hopromine ( 2 ) is ( R , R ) and was established by comparison of the reported specific rotation of the natural product with that of the synthetic one. Preparation of the characteristic bis‐8‐membered lactam scaffold was carried out by convergent build‐up of basic chiral azalactam units 21a and 21b and subsequent iterative linking ( Schemes 5 and 6 ). Key steps in the analogous syntheses of 4‐alkyl‐hexahydro‐1,5‐diazocin‐2(1 H )‐ones 21a and 21b were the introduction of the unbranched alkyl side chains into their common precursor 14 via cuprate reaction and the Sb(OEt) 3 ‐assisted cyclization of the open‐chain intermediates 20a and 20b , respectively ( Schemes 3 and 4 ). The chiral iodoester 14 was prepared from commercially available (+)‐ L ‐aspartic acid ( 12 ). Based on the synthetic strategy developed for ( R , R )‐hopromine ( 2 ), a rapid access to the parent alkaloid homaline ( 1 ) in its (±)‐form is given.