Oxidation products of arachidonic acid. IV. Model studies on the attachaient of the C(13)—C(20) side-chain in the synthesis of tetrahydrofurans and pyrans 1,2, and 3

Abstract

GEORGE JUST and DANILO CROSILLA. Can. J. Chem. 58, 2349Chem. 58, (1980 The synthesis of methyl 15-hydroxy-8(R)-methoxy-11(R)-p-nitrobenzoyloxy-9(S),12(R)-oxy-eicosa-13-ynoate, an arachidonic acid metabolite derivative, is described. As well, methods for the attachment of the C ( 1 3 j C ( 2 0 ) prostaglandin side-chain to furanosides were studied and the results are described. The reduction of the C-15 keto group on a model compound was performed and was found to have the same behavior as in the prostaglandins.A partial structure proof of Pace-Asciak's compound, 9,12-oxy-8,11,15-trihydroxy-13-enoic acid is given.GEORGE JUST et DANILO CROSILLA. Can. J. Chem. 58,2349Chem. 58, (1980. On decrit la synthkse de I'hydroxy-15 methoxy-8(R) p-nitrobenzoyloxy-ll(R) oxy-9(S), 12(R) eicosyne-13 oate de mtthyle, un derive metabolique de I'acide arachidonique. On a egalement etudie les methodes de fixation des carbones en position 13 i 20 de la chaine laterale de la prostaglandine aux furannosides et on decrit les resultats. On a realist la reduction du groupe cetonique en position 15 sur un compose type et on a trouve qu'il se comporte comme celui des prostaglandines. On donne une preuve partielle de structure du compose de Pace-Asciak, I'acide oxy-9,12 trihydroxy-8,11,15 kne-13 oique.[Traduit par le journal]In connection with the synthesis of oxidation products of arachidonic acid of type 1, 2, and 3, isolated by Pace-Asciak and Wolfe (1) and Axelrod and co-workers (2), we had to work out procedures for attaching the C(13)-C (20) side-chain to furanose derivatives (for rationale of the choice of stereochemistry of the model compounds, see refs. 1,3). In this paper, we wish to describe some model studies on this attachment and the synthesis of a derivative of type 1 having an acetylenic bond at A13, which strongly supports the structure assigned to 1.As a model, we used 1,2-0-isopropylidene-3,5,6-tri-0-methyl-a-D-glucofuranose (5); which is easily obtained by methylation (4) of the commercially available glucofuranose 4. Hydrolysis of 5 with hydrochloric acid, followed by acetylation with p-nitrobenzoyl chloride in pyridine (5) gave 7 as a mixture of anomers. Treatment with hydrogen bromide in benzene at 0°C (6) transformed 7 to bromides 8, which, when submitted to the action of mercuric cyanide in nitromethane (6), gave the Pcyanide 9 as one isomer only, as established by nmr which showed the C(l) hydrogen as a broad singlet (J,,, 2 0-1) indicating a HI,,-dihedral angle of approximately 90°C. Alkaline hydrolysis gave the cyano alcohol