Anthony Marfat

Leukotriene a: Stereochemistry and enzymatic conversion to leukotriene B

Abstract Leukotriene A was assigned the structure 5(S)- trans -5,6-oxido-7,9- trans -11,14- cis -eicosatetraenoic acid by the enzymatic conversion of a synthetic product of known stereochemistry into the naturally occurring isomer of 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid in human polymorphonuclear leukocytes.

Stereochemistry of leukotriene C-1

Abstract Leukotriene C-1, a “Slow Reacting Substance” (SRS), has been shown to possess the molecular Structure depicted by V (5(S)-hydroxy-6(R)- S -glutathionyl-7,9- trans -11,14- cis -eicosatetraenoic acid) by its identity with a totally synthetic product of known structure and stereochemistry.

A Stereocontrolled and effective synthesis of leukotriene B (1).

Abstract An efficient synthesis of leukotriene B ( 1 ) is reported which renders this important substance accessible in quantity. The process is convergent and includes a novel method for stereospecific generation of the conjugated triene unit.

Total synthesis of slow reacting substances (SRS). “Leukotriene C-2” (11-trans-leukotriene C) (3) and leukotriene D (4)

Abstract Syntheses are described for the “slow reacting substances” 11- trans -leukotriene C (3) (previously known as leukotriene C-2) and leukotriene D (4), the cys-gly analog of leukotriene C (2). The synthesized leukotrienes 3 and 4 were instrumental in the assignment of structure to these members of the family of naturally occuring slow reacting substances which includes also 2.

11-Trans leukotriene C: A naturally occurring slow reacting substance

Abstract A slow reacting substance, produced by murine mastocytoma cells, has been shown to have the structure 5(S)-hydroxy-6(R)- S -glutathionyl-7,9,11- trans -14- cis -eicosatetraenoic acid (11- trans leukotriene C, previously referred to as leukotriene C-2) by ultraviolet spectroscopy, amino acid analyses, lipoxygenase conversion and comparisions with a synthetic compound of known structure and stereochemistry.

Inhibition of leukotriene B4-induced neutrophil degranulation by leukotriene B4-dimethylamide

Abstract Leukotriene B4 (LTB4) is a potent mediator of pro-inflammatory responses including neutrophil degranulation. Leukotriene B4 dimethylamide has been synthesized and shown to inhibit neutrophil degranulation induced by LTB4. The inhibition required time to develop (∼60 secs), and had a KD of circa 2 × 10−7M, and occurred at concentrations where LTB4 dimethylamide had negligible agonist activity.

Total synthesis of 5S, 12S-dihydroxy-6,10-E,8,14-Z-eicosatetraenoic acid (5S,12S-di-HETE) (2), a new human metabolite of arachidonic acid

Abstract A synthesis of 5 S ,12 S -di-HETE ( 2 ) is reported which confirms the proposed structure and stereochemistry for this biologically active, natural eicosanoid.

Stereospecific total synthesis of 12-(r)- and 12- (s)-forms of 6-trans leukotriene B

Non enzymatic hydration of leukotriene A (1), the biogenetic precursor of leukotriene B (2) affords among other products two diastereomeric 6-trans-isomers of 2, the first stereospecific and efficient syntheses of which are recorded herein.