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. 2011 May 20;76(10):3909-16.
doi: 10.1021/jo200337v. Epub 2011 Apr 19.

Phosphate tether-mediated approach to the formal total synthesis of (-)-salicylihalamides A and B

Rambabu Chegondi  1 , Mary M L Tan, Paul R Hanson
Affiliations

Phosphate tether-mediated approach to the formal total synthesis of (-)-salicylihalamides A and B

Rambabu Chegondi et al. J Org Chem. .

Abstract

A concise formal synthesis of the cytotoxic macrolides (-)-salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4 steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol.

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Figures

Figure 1
Figure 1
Structures of two important benzolactone enamide class compounds
Scheme 1
Scheme 1
Retrosynthetic Analysis of (–)-Salicylihalamides
Scheme 2
Scheme 2
Construction of P-chiral, nonracemic bicyclo[4.3.1]phosphate (R,R,Rp)-7
Scheme 3
Scheme 3
Synthesis of Key Fragment 6
Scheme 4
Scheme 4
Formal Total Synthesis of (–)-Salicylihalamides in 13 steps from (R,R,Rp)-7 (17-LLS).
Scheme 5
Scheme 5
Regioselective Esterification Studies on Key Fragment 6
Scheme 6
Scheme 6
Formal Total Synthesis of (–)-Salicylihalamides A and B in 9 steps from (R,R,Rp)-7
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