Octreotide, a synthetic somatostatin analogue, is an octapeptide with one disulfide bridge. Crystals of octreotide are orthorhombic, space group P212121, a = 18.458 (5), b = 30.009 (7), c = 39.705 (27) A, with three molecules of octapeptide, one ordered oxalate dianion and 52 water molecules in the asymmetric unit. Complete protonation of the NH2 groups (as assumed in the refinement) would require three oxalate dianions in the asymmetric unit for charge neutrality; a chemical analysis indicated that four are present. In either case they are so disordered that they cannot be distinguished from the water molecules. The 18 951 unique reflections (Rsy m = 0.026) used for structure solution and refinement were recorded with the EMBL imaging-plate scanner using synchrotron radiation. The structure was solved by Patterson interpretation, locating the three disulfide bridges, followed by tangent phase expansion and EFourier recycling. The anisotropic refinement against all F 2 data between 1.04 and 10.0 A resolution by blocked restrained full-matrix least-squares techniques converged to a conventional R index based on F of 0.084 [I > 2a(/) and 10.0 > d > 1.04 A] and wR2, the weighted R-index on F 2, of 0.246 (for all data). One peptide molecule adopts a flat ~-sheet structure; the other two possess different irregular backbone conformations, but are similar to each other. All three molecules have a distorted type II'/3-turn around the o-Trp-Lys region, but exhibit different sidechain conformations. The crystal structure is stabilized by a network of inter-and intramolecular hydrogen bonds.

Natural Vincamine (1) has been synthesized in an enantioselective manner starting from the ethylpentenal 7. In the key step a mixture of the diastereoisomeric racemates, 14 and 15, was directly obtained from the silyl enol ether 11 and the dihydro‐β‐carboline 12 by the way of an intramolecular Mannich reaction of the intermediate 13 (Scheme 4). The undesired stereoisomers, 14 and 15b, were recycled to 15a using the related reversible Mannich reaction 18 ⇄ 14 + 15, followed by crystallization of the salt from 15a and (+)malic acid. 15a was converted to natural vincamine (1) in several steps including the known transformation 20→1.

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Addition reactions on the alicyclic double bond of eburnamenine and apovincamine SummaryThe addition of alcohols, amines or thiols on the 14,15-double bond of (-)eburnamenine (3a) or ( + )-apovincamine (9a) yielded the corresponding analogues of vincanol (5b-h), epivincanol(7b-d), vincamine (lob-e) and epivincamine (1 lb-g) with varying stereoselectivity. The reaction was achieved by addition of hydrogenbromide at -78" followed by nucleophilic attack, or in the (-)-eburnamenine series also by direct addition of alcohols and thiols under acidic conditions. Without exception the analogues of epivincamine (1 la-g) exhibited two carbonyl absorption bands in their IR. spectra. (-)-Eburnamenine (3a) was obtained from (+ )-apovincamine (9a) in a simple one pot reaction.Einleitung. -Die Alkaloide Eburnamin (6) aus Hunteria eburnea PICHON [ 11 und Vincamin (10a) aus Vinca minor L. [2] sind die Prototypen der nach ihnen benannten Indolalkaloid-Klasse Eburnamin-Vincamin [3]. Die Alkaloide dieser Klasse sind Derivate von Ringgeriisten gleicher Konstitution, namlich des 13 a-Athyl-2,3,5,6,12,13,13a, 13b-octahydro-1 H-indolo [3,2,l-de]pyrido[3,2,1-ij] [ 1, Slnaphtyridins, gelegentlich auch im ersteren Fall ccEburnan)> (2) [ 11, im letzteren ctVincan))