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Synthesis 2003(4): 0603-0622
DOI: 10.1055/s-2003-37649
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart · New York

Allyltrichlorostannane Additions to α-Amino Aldehydes: Application to the Total Synthesis of the Aspartyl Protease Inhibitors l-682,679, l-684,414, l-685,434, and l-685,458

Luiz C. Dias*, Gaspar Diaz, Andrea A. Ferreira, Paulo R. R. Meira, Edílson Ferreira
Instituto de Química - Universidade Estadual de Campinas, UNICAMP, C.P. 6154, 13084-971, Campinas, SP, Brazil
Fax: +55(193)7883023; e-Mail: ldias@iqm.unicamp.br;
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Publication History

Received 16 October 2002
Publication Date:
07 March 2003 (online)

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Abstract

The hydroxyethylene dipeptide isosteres l-682,679, l-684,414, l-685,434, and l-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-syn and 1,2-anti amino alcohols to give the diols, lactonization under TPAP conditions, lactone opening, and peptide coupling with the desired amine or dipeptide amide. The present synthetic approach represents a practical entry to a large range of other dipeptide isosteres.

Key words

amino aldehydes - HIV - peptides - total synthesis - lactones

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34

Attempts to use allylsilanes 6 and 8 with other Lewis acids (TiCl4, BF3·OEt2) as well as attempts to mix these allylsilanes and the aldehydes 13a-c before addition of SnCl4 led to poor yields, loss of the Boc protecting group, and recovered starting material.

40

Alcohols 27 and 28 have been prepared previously by Taddei and co-workers, but our 13C NMR data are not consistent with the described data reported in that work, although consistent with the expected structure. See Ref. [40]

47

After re-examining our original 13C NMR spectrum of l-685-458 (3) we observed that in our first publication in Synlett (see Ref. [25] of this manuscript) we had mistakenly referenced the central line of the residual DMSO peak at 41.9 and not 39.7, as expected.