Cicaprost

We have developed asymmetric syntheses of isocarbacyclin [3] (Scheme 1.3.2) and cicaprost [4] (Scheme 1.3.3) featuring a Cu-mediated allylic alkylation of an allyl sulfoximine [5-7] and a Ni-catalyzed cross-coupling reaction of a vinyl sulf-oximine [8-10], respectively, transformations that were both developed in our laboratories. The facile synthesis of an allyl sulfoximine by the addition-elimination-isomerization route aroused interest in the synthesis of sulfonimidoyl-sub-stituted aiiyititanium complexes of types 1 and 2 (Fig. 1.3.2) and their application as chiral heteroatom-substituted allyl transfer reagents [11]. 

Scheme 1.3.3 Asymmetric synthesis of cicaprost by the vinyl sulfoximine route.

Alkynyl iodides and bromides react smoothly with various zinc-copper organometaUics at — 60 "C leading to polyfunctional aUcynes. lodoalkynes, such as 296, react at very low temperature, but lead in some cases to copper acetylides as by-products (1/Cu exchange reaction). 1-Bromoalkynes are the preferred substrates. Corey and Helel have prepared a key intennediate 297 of the side chain of Cicaprost by reacting the chiral zinc... 

Cibenzoline [ban, inn] (clfenllne [usan]) is a cyclopropyl-imidazole derivative, a hypoglycaemic acting as a pancreatic p-cell potassium-channel blocker. It also is a cardiac depressant and can be used as an ANTIARRHYTHMIC (class la with some class III and class IV properties), cicaprost [inn] is a prostacyclin analogue, an (IP) prostanoid receptor agonist, with platelet aggregation INHIBITOR and vasodilator activity, ciclacillin [ban, inn.ian] (cyclacillin [usan]) is a semisynthetic (penicillin) ANTIBIOTIC. It can be used as an ANTIBACTERIAL to treat certain infections. 

IP Cicaprost None platelets, smooth muscle, sensory neurons smooth muscle relaxation, inhib. platelet aggregation f cAMP... 

Cicaprost by reacting the chiral zinc reagent 298 with 1-bromopropyne leading to the functionalized alkyne 299 (Scheme 7.85) [189], This cross-coupling has also been used to prepare a pheromone (300) [48d]. 

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