Ethyl cincholoiponate

Alangicine (132) has been synthesized from the acid derived from (129) by reduction and hydrolysis. This, with the appropriate /3-phenethylamine, gives the amide (131). The absolute stereochemistry of alangicine has been confirmed by its synthesis from ethyl cincholoiponate via the lactam acid (133). ... 

Meroquinenine, CgHjjOaN (meroquinene), formed by the oxidation of all four alkaloids and of cinchoninone or quininone and by the hydrolysis of quinenine or cinchenine (p. 489), crystallises from methyl alcohol in needles, m.p. 223-4° (dee.), [ajp -f- 27-5° (H2O). It gives a nitrosoamine, m.p. 67°, and a monoacetyl derivative, m.p. 110°, and can be esterified the ethyl ester hydrochloride has m.p. 165°. When oxidised by chromic acid it yields formic and cincboloiponic acids. On reduction with zinc dust and hydriodic acid, it adds on two atoms of hydrogen forming cincholoipon, CgH jOaN, and when heated with hydrochloric acid at 250-60° gives 3-ethyl-4-methylpyridine ()3-collidine). 

Prelog and Zalan have investigated the spatial distribution about positions C3, C4 and Cg and have shown that cincholoipon ethyl ester (V), whether prepared from cinchonine or quinine, has 16-7° and... 

Ankorine (92) has been synthesized from cincholoipon ethyl ester by reaction with 2-benzyloxy-3,4-dimethoxyphenacyl bromide to give (91 X = H2), followed by reduction, oxidation to the lactam by mercuric acetate and EDTA, cyclization,... 

Cincholoipon ethyl ester (168), available from the commercial Cinchona alkaloid (+)-cinchonine in 50% overall yield according to the classical... 

The natural enantiomer of A -b,enzoylhomomeroquinene [33 mp 132-134° [oc]d +64.31° (CHgOH)] and its ethyl ester [4 [a] +35.8° (CHgOH)] were synthesized by the same method starting from homo-cincholoipon ethyl ester (32) 10). 

Conclusive evidence for the cis arrangement at C.3 and C.4 was provided by Prelog and Zal4n (149). These investigators reduced cinchonine to dihydrocinchonine and converted the product by the procedure of Kaufmann, Rothlin and Brunschweiler (91) into cincholoipon ethyl ester (CVII), in which C.3 and C.4 retain the original configuration of cinchonine. Reduction of (CVII) with sodium and alcohol afforded... 

The synthesis of (-)-alangimarckine (114) from the tricyclic amino-acid (113), which had previously been prepared from cincholoipon ethyl ester (112), confirms the structure and relative stereochemistry recently deduced, " and also proves that the absolute stereochemistry is as given in (114) (Scheme 15). 

An alternative synthesis of meroquinene (D) is outlined below. A key feature of this synthesis is application of the photolytic Loffler-Freytag reaction for generating the vinyl side-chain from an ethyl group in the corresponding saturated precursor cincholoipon methyl ester. 

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