A Short Preparation of an Advanced Intermediate for Lactacystin Synthesis: The Complete Carbon Skeleton of Clasto-Lactacystin Dihydroxyacid

Abstract

An advanced intermediate 22 for lactacystin synthesis, containing the full carbon skeleton of the pyrrolidinone component, has been achieved in four steps from a protected glycine ester.

Key words

lactacystin - clasto-lactacystin - Dieckmann - acylation

References

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1

Department of Chemistry, MARA University of Technology, 40450 Shah Alam, Selangor, Malaysia.

15

Analytical data of compound 22: Colorless powder, 1:1 mixture of diastereoisomers, mp 109 °C. (Found: C, 69.26%; H, 5.98%; N, 3.10%. C₂₆H₂₇NO₆ requires C, 69.47%; H, 6.05%; N, 3.12%). IR(nujol): ν_max = 1778, 1748, 1698 cm^-1. [Found (M⁺): 449.18307. C₂₆H₂₇NO₆ requires 449.18384]. MS: m/z (%) = 449 (2) [M⁺], 394 (8), 314 (3), 91 (100), 65 (3). ¹H NMR (400 MHz, CDCl₃): δ = 1.48 (3 H, s), 1.59 (3 H, s), 1.69 (3 H, s, major), 1.72 (3 H, s, minor), 2.67 (3 H, s, major), 2.77-2.96 (4 H, m, major + minor), 3.11 (3 H, s, minor), 4.03 (1 H, d, J = 15.2 Hz, major), 4.18 (1 H, d, J = 15.2 Hz, minor), 4.51 (1 H, bs, minor), 4.56-4.57 (1 H, m, minor), 4.67 (1 H, br s, major), 4.97-4.98 (1 H, m, major), 5.06 (1 H, d, J = 12.4 Hz, minor), 5.14 (1 H, d, J = 12.4 Hz, major), 5.12-5.25 (1 H, m, minor), 5.12-5.25 (1 H, m, minor), 5.24 (1 H, d, J = 12.4 Hz, major), 5.36 (1 H, d, J = 15.2 Hz, major), 7.17-7.35. ¹³C NMR ( 100 MHz, CDCl₃): δ = 17.35 (major), 19.19 (minor), 23.73 (minor), 24.45 (major), 36.92 (major), 37.81 (minor), 44.47, 44.55, 52.19, 52.84 (OCH₃, minor), 57.59, 57.97, 68.11, 68.28, 76.11, 75.85, 118.21(minor), 118.78(major), 127.68, 127.94, 128.26, 128.29, 128.31, 128.48, 128.51, 128.53, 128.58, 128.63, 128.75, 129.08, 134.82, 135.15, 135.39, 137.83, 138.15, 164.84, 165.09, 166.72, 167.15, 170.62, 170.89, 199.95, 200.22.

16

Crystallographic data for 22 are available on request from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, fax: [phone], [e-mail], quoting the deposition number CCDC 206650.