Trachelanthic acid

Five new pyrrolizidine alkaloids, each containing a novel fourteen-membered macrocyclic ring, have been isolated by Edgar et al.x Parsonsine (44) and heterophylline (45) were present in Parsonsia heterophylla A. Cunn. and P. spiralis Wall., while spiraline (46), spiranine (47), and spiracine (48) were obtained only from P. spiralis. These five alkaloids are derived from retronecine that is esterified at C-9 with (-)-trachelanthic acid i.e. indicine), and further diesterified by a series of substituted malic acid derivatives to complete the fourteen-membered ring. Indeed, partial hydrolysis of parsonsine (44) yielded indicine (49). The non-equivalence of the C-9 protons (ABq, S 4.45 and 5.20 p.p.m.) in parsonsine indicates the presence of a macrocyclic system, and... 

Indicine JV-oxide (53) is an anti-cancer drug that is now undergoing clinical trials. Methods for its estimation include oxidation to the pyrrole derivative and treatment with Ehrlich s reagent,53 g.l.c. analysis of its trimethylsilyl derivatives,54 and differential pulse radiography.55 The aqueous degradation of indicine iV-oxide (53) to retronecine /V-oxide and (—)-trachelanthic acid has been studied.56 Indicine jV-oxide is reduced to indicine by Fem, by reduced cytochrome c, by ascorbic acid, and by denatured haemoglobin.57... 

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the fOTination 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. d76043j44 Optically active amino ketones of type (69) are inepared via acylation of dithiane with an oxazoline-protected (5)-serine methyl ester (Scheme 41). Optically active (5)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanones were prepaid by the reaction of the corresponding methyl (5)-lactate with 2-lithio-l,3-enantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bikers yeast mediated reduction. ... 

The chiral diol moiety is only rarely present as such in the final compound to be synthesized. Usually, the 1,2-diol unit is further functionalized and sometimes, can be quite difficult to find in the end-product. Nevertheless, a few natural products possess, embedded in their complex structures, an optically active vicinal diol function which has been created using the AD reaction. Such is the case for the alkaloids indicine 2 and intermedine 1, which were obtained by condensation of the nitrogen heterocycle 4 with (-1-)- and (-)-trachelanthic acid 3 and 5 respectively (Scheme 12) [79]. The desired optically active esters 8 and 9 were rapidly accessed by the AD reaction of the trisubstituted alkene 6. Dihydroxyla-tion using the AD-mix-P generated ester 7 in 83% yield and 85% ee whilst AD-mix-a gave the antipode 8 with slightly better enantioselectivity (90% ee). Hydrolysis and recrystallization furnished the optically pure acids 3 and 4 which were further transformed into the desired natural products. 

The acid components required for the synthesis of the ester alkaloids, (+)-trachelanthic and viridifloric acids, were synthesised by stereospecific routes, since the relative stereochemistry of the asymmetric centres in these acids was still uncertain. Eventually they were obtained by appropriate stereospecific icis or trans) hydroxylation of trans-2-isopropylcrotonic acid (34), and its cis-isomer obtained by photochemical isomerisation. After resolution, (+)-trachelanthic acid was identified as the t/irco-2-isopropyl-2,3-dihydroxybutyric acid (35) the corresponding erythro-isomet was identified as viridifloric acid. 

Hastanecine JV-ethochloride (XIII), C10H20CINO2 (mp 218.5°-220°) has been found esterified with trachelanthic acid in the second alkaloid, C17H32CINO5, from Lindelofia macrostpla 50) [mp 149°-151° [a]jj 20.25° (methanol)]. 

A new procedure of resolution of trachelanthic acid has been demonstrated by Kulakov et al. (144) by using the salt (mp 156°-158° [a]o — 9.4°) of (+ )-trachelanthic acid and (— )-benzylmethylamine. The previous structures advanced for trachelanthic and viridifloric acids have been confirmed by Likhosherstov et al. (145). 

The structure LXXXIX proposed previously (154a) would place this acid in this group as containing the same carbon skeleton with a carboxyl group in place of a methyl group, a relationship observed between lati-folic acid and viridifloric and trachelanthic acids (see Chart II). Wunderlich (64) has proposed an alternative structure (XCa) indicative of a relationship with the acid in retusamine (CXb) (64). 

Acetylindicine ([a],) —14.8°) was not obtained crystalline. Mild hydrolysis gave indicine, and gentle acetylation yielded diacetylindicine which on hydrogenolysis gave acetylretronecanol and monoacetyl-trachelanthic acid, which in turn was shown to be an a-hydroxy acid. 

Vol. 6, p. 75 Vol. 8, p. 50). The remaining two minor alkaloids could not be separated. Alkaline hydrolysis of this mixture gave retronecine (1), tiglic, (2S,3S)-viridifloric, and (2S,3R)-trachelanthic acids. The p.m.r. spectrum indicated that the mixture consists of symphytine (38) and a new alkaloid, myoscorpine (37), in equal amounts. 

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