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Synthesis 2003(17): 2643-2646  
DOI: 10.1055/s-2003-42426
PAPER
© Georg Thieme Verlag Stuttgart · New York

Preparation of (2,2-Dimethylhexahydrofuro[2,3-c]pyrrol-6-yl)methanol: A Conformationally Restricted Congener of Nonproteinogenic 3-Hydroxy-4-methylproline

Edwin Jao*, Stephane Bogen*, Anil K. Saksena, Viyyoor Girijavallabhan
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
Fax: +1(908)7404642; e-Mail: Stephane.bogen@spcorp.com;
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Publication History

Received 14 July 2003
Publication Date:
14 October 2003 (online)

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Abstract

Lactam 6 derived from (S)-pyroglutaminol was converted to a conformationally restricted congener of nonproteinogenic 3-hydroxy-4-methylproline. Preparation of precursor 5b was achieved via a diastereoselective epoxidation followed by a regioselective opening of the oxirane ring. Iodine-mediated cyclization was used to assemble the ether moiety of 2.

Key words

nonpeptidic - conformationally rigid - prolinol

8

The skeleton of the molecule is readily traced by HSQC, NOESY and COSY experiments. The trans nature of the epoxidation was confirmed by J(H2/H3)= ca. 0 Hz. NOE between H-3 and H-6 was detected (Figure [2] ).

9

The structure of 5a was confirmed by the presence of H3-H1a, H3-H7a, H4-H7b and a small H3-H2 NOEs (Figure [3] ).

10

The structure of 5b was confirmed by the presence of H3OH-H6, H3OH-H2, H3-H1a, H4-H1a and H6-H1a NOEs (Figure [4] ).

11

The structure of 11 was confirmed by the presence of Me9-H3, Me9-H4, Me10-H5b and H2-H5b NOEs (Figure [5] ).