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Hybridnaturstoffe: Synthese cyclischer Hydroxamsäuren der Estra‐1,3,5(10)‐trien‐Reihe
Author(s) -
ScherlitzHofmann Ina,
Dubs Manuela,
Krieg Reimar,
Schönecker Bruno,
Kluge Michael,
Sicker Dieter
Publication year - 1997
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.19970800807
Subject(s) - chemistry , moiety , ring (chemistry) , annulation , stereochemistry , medicinal chemistry , hydroxamic acid , organic chemistry , catalysis
An approach to a new class of cyclic hydroxamic acids is described leading to a formal combination of a benzoxazine subunit related to some natural aglucones occurring in plants with the steroidal skeleton from two members of the estra‐1,3,5(10)‐triene series. The annelation procedure for a 4‐hydroxy‐1,4‐oxazine moiety to the aromatic A‐ring in estrone ( 1 ) and 1‐hydroxy‐4‐methylestra‐1,3,5(10)‐trien‐17‐one ( 7 ), used as steroidal precursors, proceeds in four or three steps, respectively ( Schemes 1 and 2 , resp.). First, a 2‐nitro group is introduced regioselectively by a novel nitrosation‐oxidation procedure or by conventional nitration (→ nitrophenols 2 and 8 ). Reaction of the phenolic unit of 2 and 8 with methyl bromoacetate or ethyl chlorooxoacetate gives rise to the nitro esters 3 , 4 , 9 , and 10 , which are subjected to reductive cyclization either by means of Zn dust in ammonium chloride solution (for the acetates) or of H 2 /Pt(S)/C (for the sensitive oxalates). Hence, the novel cyclic hydroxamic acids 5 , 6, 11 , and 12 of the estra‐1,3,5(10)‐triene series are obtained.