Jeremy C. Prodger

Enantioselective Total Syntheses of Omuralide, 7-epi-Omuralide, and (+)-Lactacystin

An alkylidene carbene 1,5-CH insertion has been used as a key step in an enantioselective total syntheses of omuralide, its C7-epimer, and (+)-lactacystin. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester.

An enantioselective formal synthesis of the proteasome inhibitor (+)-lactacystin

Abstract An enantioselective formal synthesis of the proteasome inhibitor (+)-lactacystin has been achieved using an alkylidene carbene 1,5-CH insertion reaction as a key step. The key cyclisation precursor was synthesised in high diastereomeric excess using a combination of known procedures, with the two key asymmetric centres being introduced via a Sharpless asymmetric epoxidation reaction. KHMDS induced 1,5-CH insertion produced a 3-pyrroline product, which was oxidised to the corresponding 3-pyrrolin-2-one using (1) TPAP/NMO; (2) NaClO 2 ; (3) NaBH 4 . The formal synthesis was then completed with a few standard functional group interconversions.

Novel syntheses of the amino-1,2,4-triazine GW356194: identification of a synthesis amenable to scale up

Abstract New syntheses of the amino-1,2,4-triazine, GW356194 have been developed to improve on existing methodology. The use of different amidrazones in cyclisations with α-keto and α-amido carbonyl compounds as the key step for the synthesis of the 1,2,4-triazine core was evaluated and the results are presented here.

Studies on the oxidation of 2,2,4-trisubstituted 3-pyrrolines

Abstract As part of our studies directed towards a total synthesis of lactacystin, we have developed a reliable and environmentally acceptable method to oxidise 2,2,4-trisubstituted 3-pyrrolines to the corresponding 3-pyrrolin-2-ones. Several protocols were examined and the two-step (i) TPAP/NMO; (ii) sodium hypochlorite allylic oxidation was found to be the most satisfactory. Catalytic oxidation of the 3-pyrroline afforded the corresponding cyclic imine in high yield, and subsequent oxidation with NaOCl afforded the N-chloro-3-pyrrolin-2-one. The N-chloro-substituent was removed by a simple acid treatment.

Regiochemical observations on the lithiation of 1,2,4-trichlorobenzene and reaction with DMF and oxamide electrophiles in THF

Unusual regiochemistry is observed in the products arising from the reaction of lithiated 1,2,4-trichlorobenzene with N,N-dimethylformamide and tetraalkyloxamides.