Dimethyl-4-ethyl-4-formylpimelate

The known pentacyclic lactam (219), prepared from 2-hydroxytryptamine and dimethyl 4-ethyl-4-formylpimelate, has been used in an improved synthesis of ( )-quebrachamine.106a Conversion of (219) into the thiolactam, acetylation to (220), desulphurization, and hydrolysis yielded 1,2-dehydroaspidospermidine (221), which on reduction gave ( )-quebrachamine (222) (Scheme 31). A new synthesis of the tetracyclic amino-alcohols (223) constitutes another formal synthesis of quebrachamine.1066... 

The approaches to quebrachamine adopted by other workers were rather different. Pakrashi and his collaborators (281) developed a synthesis via the known pentacyclic lactam 453 (prepared from 2-hydroxytryptamine and dimethyl 4-ethyl-4-formylpimelate) and 1,2-didehydroaspidospermid-ine (27), the final stage being simply the reduction of 27 by means of potassium borohydride, as in the last stage of the original synthesis of quebrachamine by Stork and Dolfini (Scheme 43). 

Treatment of 2-hydroxytryptamine (406) with dimethyl 4-ethyl-4-formylpimelate (540) gave two isomeric oxindoles (542 and 543) differing in the stereochemistry of the ethyl group. The most polar product (542) was heated for 2 hr under nitrogen in the presence of polyphosphoric acid to afford 3-oxo- 1,2-dehydroaspidospermidine (504) in 68% yield (Scheme 32). The stereochemistry of this polar product must therefore be that... 

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