Howard E. Morton

Synthesis of α-amino and α-alkoxy aldehydes via oxoammonium oxidation

Abstract Oxoammonium oxidation (TEMPO, 1 ) of various optically active α-amino and α-alkoxy alcohols affords the corresponding aldehydes in good yield and high enantiomeric purity.

Dimethylboron bromide and diphenylboron bromide. Acetal and ketal cleavage. Cleavage of MEM, MOM, and MTM ethers.

Abstract A general and efficient procedure for the cleavage of acetals and ketals by the use of dimethylboron bromide or diphenylboron bromide is described. Under similar reaction conditions, MEM, MOM and MTM ethers also react to afford the parent alcohols in excellent yields.

Cleavage of carbonoxygen bonds. Dimethylboron bromide. A new reagent for ether cleavage

Abstract A general and efficient procedure for the cleavage of aliphatic, aromatic and cyclic ethers by the use of dimethylboron bromide is described.

Preparation of ethyl 5(s),6-epoxy-3(r)-(methoxymethoxy)hexanoate: a key chiral intermediate for mevinolin and compactin.

Abstract The synthesis of Ethyl 5(S),6-Epoxy-3(R)-(methoxymethoxy)hexanoate, a key chiral synthon for the β-hydroxy-δ-lactone portion of Mevinolin and Compactin, via a regiospecific ring opening of a tetrahydrofuran derivative by dimethylboron bromide, is described.

N-(Boc)-(L-(2-bromoallyl)-glycine : a versatile intermediate for the synthesis of optically active unnatural amino acids

Abstract N(Boc)-L-(2-Bromoallyl)-glycine ( 1 ) was synthesized from diethylacetamidomalonate and 2,3-dibromopropene in a one-pot procedure (75 % overall yield). The enantiomers were efficiently separated via a tandem biocatalytic kinetic hydrolytic resolution. 1 was elaborated to several other interesting unnatural amino acid.

Pharmacology of L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropanoic acid); a potent, selective thromboxane/prostaglandin endoperoxide antagonist

L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropa noic acid) has been studied in vitro on the guinea-pig tracheal chain, pulmonary artery and thoracic aorta ring and shown to be a potent, competitive antagonist of contractions induced by the prostaglandin endoperoxide analogue, U-44069 (pA2 values 8.0, 8.4 and 8.0 respectively). Selectivity on the guinea-pig trachea was indicated by non-competitive antagonism of contractions induced by prostaglandin D2 and minimal activity against contractions induced by leukotriene D4, prostaglandin F2 alpha, serotonin, histamine and acetylcholine. L-655,240 was a potent inhibitor of the aggregation of washed human platelets induced by U-44069 (IC50 value 7 X 10(-9) M) and inhibited aggregation of human platelet rich plasma induced by U-44069, U-46619, thromboxane A2 and collagen but not ADP or platelet activating factor. In vivo i.v. L-655,240 administered to guinea-pigs inhibited bronchoconstriction induced by i.v. U-44069 and arachidonic acid (ED50 values 0.09 and 0.23 mg kg-1) but not histamine, acetylcholine or serotonin. When administered to rhesus monkeys (3 and 10 mg/kg p.o.), L-655,240 inhibited ex vivo platelet aggregation induced by U-44069 but not ADP. It is concluded that L-655,240 is a potent, selective, orally active thromboxane/prostaglandin endoperoxide antagonist.

Efficient asymmetric synthesis of ABT-594; a potent, orally effective analgesic

Abstract A concise asymmetric synthesis of ( R )-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594) is presented in which the key intermediate t -butoxycarbonyl protected (2 R )-azetidinylalcohol is obtained in three steps from the dibenzyl ester of D-aspartic acid in 44% yield and >99% ee.

Synthetic utility of chiral tetrahydrofurans: Preparation of (1R, 3R, 5S)-1, 3-dimethyl-2, 9-dioxabicyclo[3.3.1]nonane

Abstract The use of the iodoetherification reaction for the selective preparation of optically active trans -2,4-disubstituted tetrahydrofurans and the use of the latter compounds as precursors of syn -1,3-diols is exemplified in the synthesis of (1R, 3R, 5S)- Endo -1,3-Dimethyl-2,9-Dioxabicyclo [3.3.1]nonane( 1 ).

Synthesis of α-halomethyl ketones: Oxidative hydrolysis of vinyl halides

Oxidative hydrolysis (e.g. aqueous NBS) of various vinyl halides affords the corresponding α-halomethyl ketones in good yield and purity.

The stereospecific preparation of an hydroxyethylene isostere precursor via a novel piperidine-2,5-dione template

Abstract Hydroxyethylene isostere precursor 2 was synthesized by stereochemical manipulation of a novel keto- lactam “template”. The final product was prepared in very high enantiomeric purity, in 23% overall yield from L- phenylalanine.