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

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

References

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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.