Steganone synthesis

One key step in a recent steganone synthesis is a 7 8 ring enlargement by a... 

The asymmetric total synthesis of (-)-steganone (67) was achieved through the asymmetric Mg-mediated coupling of bromide 64 and oxazoline 65, which provided a... 

In addition to the simple substitutions shown in Scheme 1, this reaction has been used in a variety of complex systems as a route to optically active substances. For example, use of chiral oxazolines in this coupling process has led to an asymmetric synthesis of (-)-steganone,3 podophyllotoxin,4 (-)-schizandrin,5 and (+)-phylictralin.6 The synthesis of (-)-schizandrin is sketched in Scheme 2. 

Retrosynthetic analysis of 5 and 6 yielded ketone 7 as pivotal intermediate. A key reaction for the synthesis of 7 was the auxiliary-controlled, di-astereoselective biaryl coupling of a phenyl magnesium bromide (from 8 or 9) with aryloxazoline 10 (Scheme 1). This coupling strategy was developed in the Meyers laboratory [12] and previously applied to the enantioselective synthesis of other naturally occurring biaryl lignans, such as steganone [13]. 

The malic acid-derived auxiliary which gives good results in the ferrocene series also looks promising among the chromium complexes, and the six-membered acetal of 400 is much more easily hydrolysed than the tartrate-derived acetals of Scheme 164 . Lithiation and bromination of 400 gives, after hydrolysis of the acetal, the complex 401 in 90% ee, increasing to >99% after recrystallization (Scheme 165). 401 is an intermediate in a formal synthesis of (—)-steganone (Scheme 182, Section III.B.2.b). 

Third, the procedure described above has been applied to the preparation of various biaryls containing hetero-aromatic rings (Entries 15-17, 19, 20). Although the number of papers reporting the use of the Ni- or Pd-catalyzed procedure for aryl-aryl coupling 1s still small, the synthesis of steganone by Raphael and his co-workers is demonstrative of its synthetic potential. 

In their synthesis of the anti-leukaemia compound steganone, Magnus, Schultz and Gallagher used the allylic alcohol 65 to make the cyclopropane 66. The extra carbon atom was incorporated into the eight-membered ring of steganone.16... 

In their total synthesis of ( )-steganone, Magnus and co-workers solved this problem via the stereoconvergent synthesis of the bicyclo[5.1.0] intermediate 106, Fig. (23) [127,128]. 

The total synthesis of racemic and later of natural (-)-steganone was described by Brown and Robin using a classical Ullmann coupling at a later stage, Fig. (25) [37,133,134,135,136], Lactone 114 was first... 

An original diastereoselective approach to the synthesis of steganone analogues was reported by Motherwell and co-workers, Fig. (29) [144], The diyne 135 was obtained from bromide 133 and lactone 134 via diastereoselective alkylation and deprotection of the alkyne groups. A cobalt-mediated [2+2+2] cycloaddition of 135 with... 

This general type of ring expansion has been put to use in the synthesis of several natural products containing eight-membered rings. One total synthesis of the antileukemic ( + )-steganone, which contains the bisbenzocyclooctadiene structure, incorporated perchloric acid catalyzed ring expansion of a substituted dibenzobicyclo[5.1.0]octane 12 as the key step. ... 

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