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. 2010 Apr 2;12(7):1556-9.
doi: 10.1021/ol1002913.

A concise, phosphate-mediated approach to the total synthesis of (-)-tetrahydrolipstatin

Phanindra K M Venukadasula  1 , Rambabu Chegondi, Soma Maitra, Paul R Hanson
Affiliations

A concise, phosphate-mediated approach to the total synthesis of (-)-tetrahydrolipstatin

Phanindra K M Venukadasula et al. Org Lett. .

Abstract

An efficient synthesis of (-)-tetrahydrolipstatin (THL) is reported. This method takes advantage of a phosphate tether-mediated, one-pot, sequential RCM/CM/hydrogenation protocol to deliver THL in eight total steps from a readily prepared (S,S)-triene. The strategy incorporates selective cross-metathesis, regioselective hydrogenation, regio- and diastereoselective cuprate addition, and Mitsunobu inversion for installation of the C5 formamide ester subunit.

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Figures

Figure 1
Figure 1
(−)-Tetrahydrolipstatin and (−)-Lipstatin
Scheme 1
Scheme 1
Retrosynthetic Analysis of (−)-Tetrahydrolipstatin
Scheme 2
Scheme 2
Stepwise RCM, CM and hydrogenation sequence
Scheme 3
Scheme 3
One-pot, Sequential CM/Hydrogenation Pathway
Scheme 4
Scheme 4
Phosphorodiamidite coupling and One-Pot, Sequential RCM/CM/Hydrogenation Sequence.
Scheme 5
Scheme 5
Total Synthesis of (−)-Tetrahydrolipstatin (1)
See this image and copyright information in PMC

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