Stephen G. Pyne

Conversion of ketones having δ, ϵ-π-functions to cyclopentanols by zinc-trimethylchlorosilane

Abstract A new method for five-membered ring annulation is described which involves free radical generation from ketones by zinc-trimethylchlorosilane followed by internal addition to a π-bond.

Total synthesis of leukotriene B5

A practical, stereocontrolled synthesis of leukotriene B5 is described which makes this substance readily available for the first time.

Total Synthesis of Uniflorine A, Casuarine, Australine, 3- epi -Australine, and 3,7-Di- epi -australine from a Common Precursor

A flexible method for the diastereoselective total synthesis of the pyrrolizidine alkaloids uniflorine A, casuarine, australine, and 3-epi-australine and the unnatural epimer 3,7-di-epi-australine from a common chiral 2,5-dihydropyrrole precursor is described.

N-Phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents

A range of N-phenethyl, N-phenacyl, and N-(1- and 2-naphthylmethyl) derivatives of 5,7-dibromoisatin 2 were prepared by N-alkylation reactions. Their activity against human monocyte-like histiocytic lymphoma (U937), leukemia (Jurkat), and breast carcinoma (MDA-MB-231) cell lines was assessed. The results allowed further development of structure-activity relationships. The compound 5,7-dibromo-N-(1-naphthylmethyl)-1H-indole-2,3-dione 5a was the most potent against U937 cells with an IC(50) value of 0.19 microM.

Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of Phytochemicals and biological activities

ETHNOPHARMACOLOGICAL RELEVANCE As many as 229 medicinal plants have been currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient of polyherbal formulations and these plants have been individually indicated for treating various types of infections including malaria, tumor, and microbial. We have focused our study only on seven species of these plants. AIM OF THE STUDY We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan selected using an ethno-directed bio-rational approach. This study creates a scientific basis for their use in the BTM and gives foundation for further phytochemical and biological evaluations which can result in the discovery of new drug lead compounds. MATERIALS AND METHODS A three stage process was conducted which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of the BTM for their mode of plant uses; (2) selecting 25 anti-infective medicinal plants based on the five established criteria, collecting them, and screening for their major classes of phytochemicals using appropriate test protocols; and (3) finally analyzing the crude extracts of the seven medicinal plants, using the standard test protocols, for their antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the ethnopharmacological uses of each plant. RESULTS Out of 25 medicinal plants screened for their major classes of phytochemicals, the majority contained tannins, alkaloids and flavonoids. Out of the seven plant species investigated for their biological activities, all seven of them exhibited mild antimicrobial properties, five plants gave significant in vitro antiplasmodial activities, two plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant showed mild cytotoxicity. Meconopsis simplicifolia showed the highest antiplasmodial activity with IC(50) values of 0.40 μg/ml against TM4/8.2 strain (a wild type chloroquine and antifolate sensitive strain) and 6.39 μg/ml against K1CB1 (multidrug resistant strain) strain. Significantly the extracts from this plant did not show any cytotoxicity. CONCLUSIONS These findings provide the scientific basis for the use of seven medicinal plants in the BTM for the treatment of malaria, microbial infections, infectious fevers, and the Trypanosoma brucei rhodesiense infection. The results also form a good preliminary basis for the prioritization of candidate plant species for further in-depth phytochemical and pharmacological investigations toward our quest to unearth lead antiparasitic, anticancer and antimicrobial compounds.

Copper-mediated cyclization-halogenation and cyclization-cyanation reactions of β-hydroxyalkynes and o-alkynylphenols and anilines

The CuX (X = I, Br, Cl, CN)-mediated cyclization-halogenation and cyclization-cyanation reactions of beta-hydroxyalkynes and o-alkynylphenol and -aniline derivatives give rise to 3-halo- and 3-cyanofuro[3,2-b]pyrroles, 3-iodo-, 3-bromo-, and 3-cyanobenzofurans, and 3-cyanoindoles, respectively.

Diastereoselective Reactions of Sulfoximines

Abstract This review will deal exclusively with the diastereoselective reactions of chiral sulfoximine reagents that lead to the formation of new chiral C-C, C-N, and C-O bonds. The diastereoselective reactions of lithiated sulfoximines with electrophiles, including carbonyl compounds, imines, Michael acceptors and alkyl halides are discussed. The diastereoselective conjugate addition reactions of vinyl sulfoximines with various carbon, nitrogen and oxygen nucleophiles are also addressed. A number of studies reported here were performed on racemic substrates but only one enantiomer has been shown to assist the reader.

Influence of the chiral dopant anion on the generation of induced optical activity in polyanilines

Abstract Emeraldine base (EB) is doped with (1S)-(+)-3-bromocamphor-10-sulfonic acid and a novel chiral acrylamidesulfonic acid (4) in NMP and DMF solvents to give new optically active polyaniline salts (PAn.HA). The conjugate base anions (A − ) of these chiral dopants (as with the previously studied (+)-camphor-10-sulfonic acid, HCSA) contain SO 3 − and carbonyl (C=O) groups that may maintain the polyaniline chains in a preferred one-sense helical screw via simultaneous electrostatic and H-bonding. Optically active polyaniline salts are also produced via analogous doping of EB (in NMP or DMF) with the chiral dicarboxylic acids (+)- or (−)-tartaric acid and O,O′-dibenzoyl- d -tartaric acid, which possess quite different structural motifs to HCSA. A common feature of all the dopants successful in generating optically active polyaniline salts is their bidental nature, allowing attachment of the dopant to the polymer backbone at two places simultaneously.

Synthesis of (+)-uniflorine A: a structural reassignment and a configurational assignment

The total synthesis of (+)-uniflorine A has allowed for the structural reassignment and the configurational assignment of the alkaloid (-)-uniflorine A from a 1,2,6,7,8-pentahydroxyindolizidine structure to (-)-(1 R,2 R,3 R,6 R,7 S,7a R)-1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine (6- epi-casuarine).

Synthesis of a new series of potent inhibitors of thromboxane A2 biosynthesis

Abstract The pyridino prostanoids 9 , 12 and 14 have been synthesized (in racemic form) and have been found to be effective inhibitors of the biosynthesis of thromboxane A 2 in human platelets (IC 50 1–3 μM).