Paul R. Jenkins

The regiospecific Fischer indole reaction in choline chloride·2ZnCl2 with product isolation by direct sublimation from the ionic liquid

The Fischer indole synthesis occurs in high yield with one equivalent of the ionic liquid choline chloride[middle dot]2ZnCl(2); exclusive formation of 2,3-disubstituted indoles is observed in the reaction of alkyl methyl ketones, and the products readily sublime directly from the ionic liquid.

Reassessment of the Reaction Mechanism in the Heme Dioxygenases

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme enzymes that catalyze the O(2)-dependent oxidation of L-tryptophan to N-formyl-kynurenine. Previous proposals for the mechanism of this reaction have suggested that deprotonation of the indole NH group, either by an active-site base or by oxygen bound to the heme iron, as the initial step. In this work, we have examined the activity of 1-Me-L-Trp with three different heme dioxygenases and their site-directed variants. We find, in contrast to previous work, that 1-Me-L-Trp is a substrate for the heme dioxygenase enzymes. These observations suggest that deprotonation of the indole N(1) is not essential for catalysis, and an alternative reaction mechanism, based on the known chemistry of indoles, is presented.

Ring-closing metathesis in carbohydrate annulation

Even eight-membered rings (such as in 2) can be formed by ring-closing metathesis of glucose derivatives such as 1. Enantiomerically pure tricyclic spiro compounds can also be prepared.

Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4

We present the design, synthesis and biological activity of a library of substituted (biphenylcarbonyl)-tryptamine and (biphenylcarbonyl)-tetrahydro-beta-carboline compounds related to the natural product fascaplysin, as novel inhibitors of CDK4/cyclin D1. We show all these molecules, prepared using the Suzuki-Miyaura reaction, being selective inhibitors of CDK4 over CDK2. The most active compounds have a CDK4 IC(50) in the range 9-11 microM, three of them containing the para-biphenyl plus para-substituents supporting the existence of a pi-stacking pocket within the active site of CDK4.

Fascaplysin-inspired diindolyls as selective inhibitors of CDK4/cyclin D1

We present the design, synthesis and biological activity of a new series of substituted 3-(2-(1H-indol-1-yl)ethyl)-1H-indoles and 1,2-di(1H-indol-1-yl)alkanes as selective inhibitors of CDK4/cyclin D1. The compounds were designed to explore the relationship between the connection mode of the indolyl moieties and their CDK inhibitory activities. We found all the above-mentioned designed compounds to be selective inhibitors of CDK4/cyclin D1 compared to the closely related CDK2/cyclin A, with IC(50) for the best compounds 10m and 13a being 39 and 37microm, respectively.

Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-β-carbolines

The synthesis of a series of beta-carboline-based analogues of the natural product fascaplysin is presented; the compounds were produced using a novel photo-oxidation reaction of 1-benzyl-4,9-dihydro-3H-beta-carbolines as the key step.

Why is vinyl anion configurationally stable but a vinyl radical configurationally unstable

Abstract A qualitative explanation of the configurational stability of vinyl anions and the configurational instability of vinyl radicals is given.

An intramolecular Diels–Alder approach to forskolin

A Diels–Alder route to two tricyclic lactoes with the same relative stereochemistry as C-1 and C-10 in forskolin is described.

The first example of a highly stereoselective intramolecular radical cyclisation of a cyclopentenol derivative

Abstract Silyl methylene radical cyclisation of a β-allylic cyclopentaannulated derivative of glucose leads to a single cis fused tricyclic ring system whereas the same cyclisation of the corresponding α derivative leads to a mixture of cis and trans fused products. These results can be explained by the preference for the formation of the cis fused 5,6-ring system even when this does not involve reaction from the least hindered side of the molecule.

Synthesis of the taxane ring system using an intramolecular Diels-Alder reaction of a 2-substituted diene

A synthesis of (1R/S,3R/S,8S/R)-8-methyltricyclo[9.3.1.03,8]pentadec-11-en-2-one, which is the ring system of the taxane natural products and contains 3 chiral centres having the required relative configuration, is described.