Isodihydrocyclomicrophylline A fromBuxus sempervirens

Chemistry of Natural Compounds
1993.0

Abstract

As a result of further studying the alkaloids of Buxus sempervirens L. cultivated in the environs of Tashkent, a new alkaloid, isodihydrocyclomicrophylline A (C28H50O2N2, mp 215-217°C (ethanol), [α]D -64.27°C (c 0.527; chloroform)), was isolated. Its IR spectrum showed characteristic absorption bands at 3368, 3047, and 1452 cm-1 (methylene of a cyclopropane ring and active hydrogens). The NMR spectrum exhibited nine-proton singlets at 1.15, 1.06, and 0.92 ppm (three -C-CH3 groups), a twelve-proton singlet at 2.32 and 2.18 ppm (two N-dimethyl groups), a three-proton doublet at 0.97 ppm (J = 7.52 Hz, a C-CH3 group), a one-proton multiplet at 4.09 ppm (-CH-OH, characteristic for 16β-proton of Buxus alkaloids), and a two-proton quartet at 3.25 and 3.02 ppm (-CH2-OH). The mass spectrum had main peaks at m/z 57, 58, 70, 71, 72 (100%), 84, 98, 342, 383, 424, and 466 (M+), with m/z 72 confirming a dimethylamino group at C20 of the pregnane nucleus. Acetylation of (I) with acetic anhydride in pyridine yielded O,O'-diacetylisodihydrocyclomicrophylline A (C32H54O4N2, mp 187-189°C (acetone), [α]D -89.61° (c 0.905; chloroform)), whose IR spectrum lacked active hydrogen bands but showed O-acetyl absorption at 1743 cm-1. Its NMR spectrum had signals at 0.86, 1.02, 1.13 ppm (s, 9H, -C-CH3), 0.94 ppm (d, 3H, C-CH3, J = 6.51 Hz), 2.24, 2.06 ppm (s, 12H, 2(CH3)2), 5.14 ppm (m, 1H, -HC-O-acetyl), and 3.49, 3.32 ppm (quartet, 2H, center at 3.40 ppm, J = 11.82 Hz, -H2CO-acetyl), with mass spectral main peaks at m/z 70, 71, 72 (100%), 84, 371, 386, 442, 512, 530 (M+). Comparison of (I) and its acetyl derivative with dihydromicrophylline A and its acetate revealed differences in specific rotations, melting points, and proton chemical shifts of secondary/tertiary methyl groups, indicating (I) is an iso product of dihydrocyclomicrophylline A, likely at C-4 or C-20. The most probable structure and configuration is 3β,20α-bisdimethylamino-16α-hydroxy-4α-hydroxymethyl-4β,14β-dimethyl-9β,19β-cyclo-5α-pregnane.

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