Nauclefine synthesis

In continuation of the nauclefine synthesis, Sainsbury and Uttley (123) unsuccessfully investigated the regioselectivity of the photocyclization of the enamide 201 and the bromoenamide 203 though a regioselective formation of the nauclefine-type product (Scheme 79). 

Fused pyranone derivatives are converted into the corresponding fused pyridone derivatives by the action of an appropriate amine. Thus, heterocycle (308) yields naphthyridone (417) in moderate yield when reacted with ethanolic ammonia solution <62JCS4528>. Compound (418) and tryptamine gives the indole derivative (419) (82% yield) <76H(4)247>, which was used in the synthesis of nauclefine (420), and compound (421) and tryptamine gave heterocycle (422) (80% yield) <75H(3)627>, which was used in the synthesis of angustine (423). 

Nauclefine. In 1975 Sainsbury and Webb (122) and Hotellier et al. (71) reported the isolation and synthesis of nauclefine. Hotellier et al. (71) obtained nauclefine in 6% by treating harmalane with an excessive amount of nicotinoyl chloride. Alternatively, Sainsbury and Webb (122) carried out photocyclization of the enamide 201, prepared from harmalane and the above acid chloride, to obtain a mixture of two lactams, 29 and 202, in the ratio of 100 9, with 48% yield. The major product thus obtained was identical to parvine, whose name was first proposed by Sainsbury (122) but later changed to nauclefine (123) (Schemes 77 and 78). 

As in the azaberbine synthesis described in Section IV,C, Ninomiya el al. (68) prepared the spirodihydropyridine 206 by acylation of harmalane with an excessive amount of isonicotinoyl chloride and then synthesized nauclefine (29) by photorearrangement of the corresponding N- nor derivative 207 (Scheme 81). 

From a pharmacological point of view, Shafiee (125) investigated an effective synthesis of thia analogs of angustidine, angustoline, nauclefine, and naucletine (Scheme 83). 

The structure of angustoline has been confirmed by a brief synthesis (Scheme ll), in which the crucial stage involved the (non-regiospecific) photochemical dehydrogenative cyclization of the amide (58). Nauclefine was similarly synthesized... 

The considerable amount of new synthetic work reported in this area during the past year includes a new synthesis of nauclefine (72) by a modification of the enamide photocyclization route. The reaction of harmalan (73) with an excess of isonicotinoyl chloride gave the spirodihydropyridine derivative (74), which on hydrolysis followed by irradiation gave nauclefine (72) (Scheme 8). 

Full details of Sainsbury s synthesis of nauclefine " have now been published. ... 

A variation on Ninomiya s enamide photocyclization strategy is illustrated in the synthesis of nauclefine (382) (Scheme 3.65) (62). Condensation of har-malane (336) and isonicotinyl chloride (379) afforded spirocycle 380 which was hydrolyzed to pentacyclic enamide 381. Irradiation of 381 yielded target 382. 

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