David A. Clark

Structure of leukotriene c identification of the amino acid part

Abstract Leukotriene C, a “Slow Reacting Substance” (SRS) from mouse mast cell tumors, was earlier shown to be a derivative of 5-hydroxy-7,9,11,14-eicosatetraenoic acid with a cysteine containing substituent in thioether linkage at C-6 (Murphy, R.C., Hammarstrom, S., Samuelsson, B.: Proc. Natl. Acad. Sci. USA, 76 , 4275–4279 (1979)). The substituent has now been identified as γ-glutamylcysteinylglycine (glutathione).

Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity.

Abstract A third major chemical constituent of slow reacting substance (SRS-A) has been shown to possess the chemical structure 5(S)-hydroxy-6(R) S -cysteinyl-7,9- trans -11,14- cis -eicosatetraenoic acid (leukotriene E). Comparison of the biological activities of leukotriene E and the 11- trans stereoisomer on guinea pig airways, ileum, and cutaneous microvasculature has revealed a noteworthy dependence of activity on stereochemistry with leukotriene E being much more potent in each system.

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.

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.

A new method for the synthesis of 2-pyridinethiol carboxylic esters

Abstract An effective and convenient synthesis of 2-pyridinethiol esters of carboxylic esters has been developed which involves the interaction of a carboxylate salt with the S-chloroformyl derivative of 2-pyridinethiol.

Synthesis of two position isomers of leukotriene C having the S-peptide at C(12)

Abstract Two positional isomers of leukotriene C(1) (4a,4b), previously considered as possibly being members of the family of slow reacting substances, have been synthesized and found to be biologically inactive.

Studies on the total synthesis of rifamycin. A method for the closure of the macrocyclic unit

Abstract The formation of the macro ring of rifamycin S ( 1 ) has been accomplished by generating the lactam linkage through cyclization of a suitably protected and activated amino acid ( 4 ).