Richard G. Powell

Structure-activity study of cytotoxicity and microtubule assembly in vitro by taxol and related taxanes.

Abstract Structure-activity relationships of natural and semisynthetic taxanes are reported. Activity is measured in vivo by cytotoxicity toward the macrophage-like cell line J774.2, and in vitro by promotion of microtubule assembly in the absence of exogenous GTP and by inhibition of [3H]taxol binding to microtubule protein. Cytotoxicity and in vitro activity require both an intact taxane ring and ester side chain at position C-13. Addition of acetyl moieties at positions 2′ and 7 results in loss of in vitro activity but not cytotoxicity.

Structures of homoerythrina alkaloids from cephalotaxus harringtonia

Abstract The structures of five minor alkaloids from Cephalotaxus harringtonia K. Koch var. harringtonia have been determined. These alkaloids are simple derivatives of schelhammericine (I). In alkaloid II, the methylenedioxy group of I is replaced by one hydroxyl group and one methoxyl group; alkaloid III is the analogous dimethoxy derivative. Alkaloids IV, V and VI are the corresponding C-3 epimers of alkaloids I, II and III. Though schelhammericine itself has not yet been observed in Cephalotaxus, alkaloids IV and V are identical in all respects with two alkaloids found in Schelhammera pedunculata. Alkaloids II, III and VI are previously unreported in the literature. The co-occurrence of these minor homoerythrina-type alkaloids (II-VI) with the major Cephalotaxus alkaloid cephalotaxine (VII) and its antileukemic esters (VIII-XI) is of interest biogenetically.

Deoxyharringtonine, a new antitumor alkaloid from Cephalotaxus: Structure and synthetic studies☆

Abstract A new alkaloid (proposed name, deoxyharringtonine) with significant antileukemic activity has been isolated from Cephalotaxus harringtonia (Forbes) K. Koch var. harringtonia cv. Fastigiata. Its structure has been established as either 2 or 3 by chemical and spectral methods. Total synthesis of the dicarboxylic acid side chain and esterification of its primary carboxyl group with natural cephalotaxine ( 1 ) yields 3 : therefore, deoxyharringtonine must be 2 .

Sesbanimide A and related tumor inhibitors from Sesbania drummondii: Structure and chemistry

Extracts of Sesbania drummondii seed have yielded three new glutarimide tumor inhibitors which are markedly active in the PS leukemia (in vivo) system and in the KB cell culture system. Structures of sesbanimide A, sesbanimide B, sesbanimide C, acetylation products of the sesbanimides and five compounds obtained by hydrogenating sesbanimide A under mild conditions have now been established using high-field 1H NMR, 13C NMR and mass spectral correlations. Treatment of sesbanimide A diacetate with sodium bicarbonate in aqueous methanol gives rapid elimination of acetic acid and two subsequent products derived via solvolysis of the glutarimide ring.

ALKALOIDS OF CEPHALOTAXUS WILSONIANA

Abstract Four alkaloids have been isolated from extracts of Cephalotaxus wilsoniana Hayata. The major alkaloid (I), for which the name wilsonine is proposed, occurs with its C-3 epimer (II); in addition to these homoerythrina alkaloids, minor amounts of cephalotaxine (III) and acetylcephalotaxine (IV) are also found.

A secoisolariciresinol branched fatty diester from Salvia plebeia seed

Abstract The structure of a second new lignan diester from Salvia plebeia seed has been determined. Hydrolysis of this diester yields two compounds, 12-methyltetradecanoic acid and secoisolariciresinol.

Structure of a secoisolariciresinol diester from Salvia plebeia seed

Abstract The structure of a unique lignan diester from Salvia plebeia seed has been determined. Hydrolysis of the diester yields ferulic acid, (+)-l2 l -methyltetradecanoic acid and secoisolariciresinol.

Cephalomannine; a new antitumour alkaloid from Cephalotaxus mannii

Chemical investigation of the antileukaemic and cytotoxic principles of Cephalotaxus mannii has led to the isolation and characterization of cephalomannine, an alkaloidal taxane derivative structurally unrelated to the harringtonine series of alkaloids characteristic of most Cephalotaxus species.

Antitumor Agents from Higher Plants

Various plant preparations have been recommended for treatment of warts, tumors and cancerous growths throughout recorded history. In a classic survey of the available literature, Hartwell1 identified over 3,000 plants reported to be of use in the treatment of these maladies. Numerous plant extracts have been subjected to detailed testing and fractionation studies in recent years and a wide variety of new active compounds have been isolated. Many of these new materials show promising antitumor activity in animal test systems and in preliminary clinical trials.