The Isolation of Neoprotoveratrine and Protoveratrine from Veratrum viride Ait.

Klohs, M. W.; Arons, R.; Draper, M. D.; Keller, Fred S.; Köster, Sandra; Malesh, W.; Petracek, F. J.

doi:10.1021/ja01140a033

Cited by 19 publications

(6 citation statements)

References 2 publications

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“…Whereas the protoveratrines were easily isolated from V. album , it was not until 1952 that this group of compounds, along with another ester, termed neoprotoveratrine, was identified in V. viride (Klohs et al 1952). Rather, investigations by Fried et al (1949, 1950) found that the principal alkaloids responsible for the hypotensive effects of V. viride were esters of germine, coined germidine and germitrine.…”

Section: Modern Phytochemistry and Use Of Veratrum Alkaloids In The Tmentioning

confidence: 99%

Medicinal history of North American Veratrum

Chandler

McDougal

2013

Phytochem Rev

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Plants belonging to the genus Veratrum have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in Veratrum species, some of which are potent bioactives. This review discusses Veratrum species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus Veratrum (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the Veratrum plants of North America and the medicinal uses of their bioactive steroidal alkaloids.

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Section: Modern Phytochemistry and Use Of Veratrum Alkaloids In The Tmentioning

confidence: 99%

Medicinal history of North American Veratrum

Chandler

McDougal

2013

Phytochem Rev

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“…(3) The 3,15-diesters bearing branched-chain acid residues at position 15 were more active than those with straight chain acid residues.14 (4) The ester grouping at position 3 need not be branched. Neogermitrine, one of the most active of the naturally-occurring esters, is germine 3,7-diacetate 15-( -)-2/-methylbutyrate.16…”

mentioning

confidence: 99%

“…Protoverine 3,6,15-triisobutyrate 7-acetate {VII). Methanolysis of (V) (1)(2)(3)(4)(5)(6)(7)(8) g) by the procedure described for the preparation of (VI) yielded (VII) (760 mg) in the form of colourless needles.…”

mentioning

confidence: 99%

Veratrum Alkaloids--XLIV. Structure-Activity Relationships in a Series of Synthetic Hypotensive Esters of Protoverine

Kupchan¹,

Hensler²,

Weaver³

1961

J. Med. Chem.

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A study aimed at further elucidation of the relationship between hypotensive activity and structure among analogs of the protoveratrines is reported. A series of synthetic protoverine tetraesters, which differ from each other only in the nature of the acid residue affixed at 6 5 , have been prepared and subjected to preliminary phatmacological evaluation. The results indicate that alteration in the structure of the ester affixed at C16 in analogs of the protoveratrines profoundly affects hypotensive potency.wo recent developments have stimulated Tstudies involving the synthesis and pharmacological evaluation of analogs of the protoveratrines. On the chemical side, our elucidation of the complete structures and configurations of protoveratrine A (I) and protoveratrine B (11) (1) and several related hypotensive ester alkaloids (2, 3) made feasible the systematic alteration of the molecules. On the clinical side, recent work has demonstrated significant differences between protoveratrine A and protoveratrine B when the substances are administered orally, particularly with regard to hypotensive-emetic relationships (4-6). Since protoveratrines A and B differ only in the nature of the ester moiety a t C3, it was deemed desirable that new protoverine (111) (7) esters, which differ from the protoveratrines solely in the nature of the acid residues, should he prepared and subjected to pharmacological evaluation.In our previous studies the compounds examined were protoverine derivatives with varying substitution a t positions 3, 4, 6, 7, 14, 15, and 16 (8-10). The results supported the following generalizations (a) esterification a t position 16 with acetate or isobutyrate is accompanied by a profound loss in activity, (b) esterification a t positions 3 and 15 is required for high activity, chain acid may be disadvantageous, (g) oxidation of the alcohol group at position 16 to a ketone group is accompanied hy a loss in activity, (lz) acetonide formation a t positions 14 and 1.5 is accompanied by a profound loss in activity, (i) esterification a t position 3 may he disadvantageous, and ( j ) considerable alteration can be made in the structure of the ester affixed a t 3 without greatly altering hypotensive potency. In view of the aforementioned facts that minor differences in the ester affixed a t 3 significantly affect the hypotensive-emetic ratio of the protoveratrines and that changes in the structure of the ester at C3 do not greatly alter hypotensive potency, it was deemed desirable that additional compounds which differ from each other only in the nature of the ester a t C15 should be prepared and subjected to pharmacological evaluation. The present report details the synthesis and preliminary pharmacological evaluation of three new analogs of the protoveratrines In the new analogs, the isohutyrate residue, previously demonstrated to he an effective suhstitute for the naturally-occurring substituted a-niethylhutyrate residues (S), is affixed a t C3 Treatment of protoverine (111) with acetone and hydrochloric ac...

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“…Anal. Caled, for C13Hle02: C, 76.44; , 7.90. Found: C, 76.31, 76.41; , 8.07, 8.10. Although several attempts were made to obtain solid derivatives of XII, these were unsuccessful.…”

mentioning

confidence: 99%