Synthetic studies in the field of the curare alkaloids

By oxidation and the identification of the oxidation products, it has been shown that the -[4-(2-alkoxy-5-alkoxycarbonylmethylphenoxy)-3-methoxyphenyl] ethylamides of 4-benzyloxyphenylacetic acid obtained previously and differing in their physicochemical properties are based on the same skeleton and differ only in their spatial configuration, since on Bischler-Napieralski cyclization they give isomeric dihydroisoquinoline compounds. The structure of the latter was established by oxidation to the isomeric acids 2,2-dimethoxy-3,4,5-tricarboxy(diphenyl ether) and 2,2-dimethoxy-4,5,5-tricarboxy-(diphenyl ether); the latter is identical with the compound obtained by the degradation of the methyl ester of natural tubocurarine. 1-(4Benzyloxybenzyl)-6-methoxy-7-(2-methoxy-5-methoxycarbonyl methylphenoxy)-N-methyl-1,2,3,4-tetrahydroisoquinoline and a compound isomeric with it have also been synthesized, and the former has been shown to be identical with a substance obtained by independent synthesis from the 4-benzyl ether of N-methylcoclaurine. During the synthesis of the latter it was shown that cyclization takes place unambiguously without the formation of isomeric compounds.For part XIII, see [2].     

Researches on synthetic curare alkaloids

The dimethyl ether of racemic lyenzinine is synthesized by sucessive building-up of tetrahydroisoquinoline bases. The utility of this method for preparing hydroxy compounds is demonstrated. The benzyl analog of the diacetate of bisdehydroisolyenzinine is synthesized.For Part XVIII see [1].     

Synthetic researches in the field of curare alkaloids XVII. Synthesis of 1-(3′-bromo-4′-methoxybenzyl)-6-methoxy-7-hydroxy-n-methyl-1, 2,3, 4-tetrahydroisoquinoline

1-(3′-Bromo-4′-methoxybenzyl)-6-methoxy-7-hydroxy-N-methyl-1, 2,3, 4-tetrahydroisoquinoline is synthesized. It is an intermediate in preparing bisbenzylisoquinoline alkaloids of the gaiatin and dauritsin type.     

Synthetic entry into the secoisoquinoline alkaloids

Several analogs of secoisoquinolinc alkaloids bearing a dimethylaminoethyl side chain and a benzilic, or reduced benzilic group were synthesized. Two independent methods based on the intermediacy of 1,3-dithians and O-benzoylated cyanohydrins as acyl anion equivalents were used.     

Synthetic investigations of (1,3′)-bistetrahydroisoquinolines: towards pentacyclic analogues of piperazine core alkaloids

Synthetic investigations of (1,3′)-bistetrahydroisoquinolines are reported as the key intermediates for the synthesis of ecteinascidin and phthalascidin pentacyclic structure analogues through successive Pictet-Spengler cyclization and intramolecular peptide coupling. The direct Pictet-Spengler reaction between a derivative of l-DOPA and N-protected-α-aminoaldehyde was first extended to the synthesis of cis-(1,3′)-bistetrahydroisoquinoline. After introduction of the required amino acid moiety, an efficient six-membered ring intramolecular peptide coupling gave rise to piperazine derivative structures. Complete structural assignments were corroborated by NMR and X-ray spectroscopic methods. Nevertheless, the optical integrity of the N-protected-α-aminoaldehyde seems to be sensitive to the reaction conditions. Pentacylic structures, having an anti C3-C11 backbone stereochemistry, were obtained from cyclization para- and ortho- to the 3-OH group of the l-DOPA derivative.     

Synthetic studies toward lapidilectine-type Kopsia alkaloids

A rapid synthesis of the tetracyclic core of Kopsia indole alkaloids related to lapidilectine B, grandilodine C, and tenuisine A is reported. Key to the success of this route was an efficient and scalable Ugi four-component coupling to install all the necessary carbons found in the natural products.     

Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids

Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting collection of halogenated cytotoxic agents derived from tyrosine which feature an array of reactive functional groups. Herein we explore chemical and potentially biosynthetic relationships between architecturally complex gymnastatin and dankastatin members, finding conditions that favor formation of a given scaffold from a common intermediate. Additionally, we find that multiple natural products can also be formed from aranorosin, a non-halogenated natural product also produced by Gymnascella sp. fungi, using simple chloride salts thus offering an alternative hypothesis for the origins of these compounds in nature. Finally, growth inhibitory activity of multiple members against human triple negative breast cancer cells is reported.

Total synthesis sheds light on biosynthetic relationships among the chlorinated gymnastatin and dankastatin alkaloids.     

Synthetic strategies to the ergoline ring system of ergot alkaloids

The synthetic strategies to the ergoline ring system (I) have been outlined, and discussed in terms of their yields and limitations. The total syntheses of ergoline, racemic and natural dihydrolysergic acid, lysergic acid, isosetoclavine, penniclavine, elymoclavine and chanoclavine-I have been described. These illustrate the synthetic problems that have been encountered in ergoline chemistry. The role of key intermediates has been emphasised. Modification to the original schemes have not given yields or procedures that can compete with the production by fermentation of ergot alkaloids. However, it is hoped that the synthetic strategies discussed in this article will provide useful information, when considering new approaches, or modification, to the unique heterocyclic ring system of ergoline.     

Synthetic analogues of Peganum alkaloids VII. Bromine-substituted quinazoline alkaloids and their analogues

The quinazoline bases pentamethylenequinazoline and peganol react with bromosuccinimide in glacial acetic acid to form the corresponding 6-bromoquinazoline derivatives. Some by-products of the bromination reaction have been isolated and characterized. 6-Bromopeganol has been subjected to x-ray structural analysis.Institute of Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 233–240, March–April, 1992.     

Synthetic studies on terpenoids—III: Synthetic approaches to diterpene alkaloids

A stereoselective synthetic route to the bicyclic keto ester 14 from octalin 4 is described. Ketoester 14 is converted to its azide 27 in several steps. Photolysis of 27 produced the lactam 2 whose transformation to lactam 3 is reported.     

Synthetic studies in the field of chlorobium chlorophyll

By the condensation of -halogenomethyl derivatives of pyrroles with -unsubstituted pyrroles the synthesis of the following unsymmetrical dipyrrolylmethanes has been effected: 5-benzyloxycarbonyl-5-ethoxycarbonyl-3, 3-di(-methoxycarbonylethyl)-4,4-dimethyl-2,2-dipyrrolylmethane (IIIa), 5-benzyloxycarbonyl-5-ethoxycarbonyl-3-(-methoxycarbonylethyl)-4, 4-diniethyl-3-n-propyl-2,2-dipyrrolylmethane(IIIb), 3-acetyl-5-benzyloxycarbonyl-4-ethyl-5-methoxycarbonyl-3, 4-dimethyl-2,2-dipyrrolylmethane (IIIc), and 3-bromo-5-benzyloxycarbonyl-4-ethyl-5-methoxycarbonyl-3, 4-dimethyl-2,2-dipyrrolylmethane (IIId). Hydrogenation of the unsymmetrical dipyrrolylmethanes IIIa, b, c, and d has given the corresponding monocarboxylic acids IVa, b, c, and d. The formylation of the dipyrrolylmethanemonocarboxylic acid IVa has given 5-ethoxycarbonyl-5-formyl-3,3-di(-methoxycarbonylethyl)-4, 4-dimethyl-2,2-dipyrrolylmethane (V).For communication II, see [1].Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 8, pp. 1045–1047, August, 1970.     

Synthetic RCM approaches to enantiopure polyhydroxylated pyrrolizidine alkaloids

RCM approach to hindered 5-5-fused bicyclic pyrrolizidine system starting from chiral pyrrolidine, obtained from d-(+)-mannose, has been achieved in convenient yield.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 465–469, July–August, 1986.