Substrate Directable Heck-Matsuda Reactions: A Short and Stereoselective Total Synthesis of S1P1 Agonist

Substrate Directable Heck-Matsuda Reactions: A Short and Stereoselective Total Synthesis of S1P1 Agonist

Oliveira, Caio C.; Santos, Emerson Andrade Ferreira dos; Correia, Carlos Roque Duarte

Abstract:

Selective agonists for the sphingosine-1-phosphate receptor subtype 1 (S1P1) constitutes an important class of drugs for the treatment of multiple sclerosis. In 2007, the aminoalcohols 1a-b were rationally designed to act as S1P1 orally active agonists. The two isomers show good activity in vitro, but compound 1b was more active in in vivo tests. In order to obtain these molecules and new analogs we decided to employ the practical and effective Heck-Matsuda reaction as a key step in their synthesis.

Selective agonists for the sphingosine-1-phosphate receptor subtype 1 (S1P1) constitutes an important class of drugs for the treatment of multiple sclerosis. In 2007, the aminoalcohols 1a-b were rationally designed to act as S1P1 orally active agonists. The two isomers show good activity in vitro, but compound 1b was more active in in vivo tests. In order to obtain these molecules and new analogs we decided to employ the practical and effective Heck-Matsuda reaction as a key step in their synthesis.

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DOI: 10.5151/chempro-14bmos-R0163-1

Referências bibliográficas

• [1] 1 Strader, C. R.; Pearce, C. J. and Oberlies, N. H. J. Nat. Prod., 2011, 74, 900-907
• [2] 2 Zhu R.; Snyder, A.H.; Kharel, Y.; Schaffter, L.; Sun, Q.; Kennedy, P.; Lynch, K. and Macdonald, T. L. J. Med. Chem., 2007, 50, 6428–6435 3 Lebel, H. and Leogane, O. Org. Lett., 2006, 7, 4107-4110.

Como citar:

Oliveira, Caio C.; Santos, Emerson Andrade Ferreira dos; Correia, Carlos Roque Duarte; "Substrate Directable Heck-Matsuda Reactions: A Short and Stereoselective Total Synthesis of S1P1 Agonist", p-163-163. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 1, Setembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-14bmos-R0163-1