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A Concise Synthesis of Tubuphenylalanine and Epi-Tubuphenylalanine via a Diastereoselective Mukaiyama Aldol Reaction of Silyl Ketene Acetal

Yunjeong Park, Mikyung Sim, Tong-Shin Chang, Jae-Sang Ryu

Org Biomol Chem. 2016 Jan 21;14(3):913-9.

PMID: 26608925

Abstract:

We have developed a straightforward and auxiliary-free synthetic route towards tBu-tubuphenylalanine (tBu-Tup) and tBu-epi-tubuphenylalanine (tBu-epi-Tup), which are the key components of tubulysins and their analogs. A Lewis acid-mediated diastereoselective Mukaiyama aldol reaction using silyl ketene acetal and N-Boc-L-phenylalaninal provided γ-amino-β-hydroxyl-α-methyl esters, which were deoxygenated to γ-amino-α-methyl esters under Barton-McCombie deoxygenation conditions. Notably, the desired tBu-Tup and tBu-epi-Tup were obtained in good overall yields in four steps.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP72155454 N-Boc-L-phenylalaninal N-Boc-L-phenylalaninal 72155-45-4 Price
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