Oxidative Reactions of Azines. 6. Lactamization of 4-Aryl- and 4-Phenethenyl-substituted 1,2,3,6-Tetrahydropyridines and Dihydroxylation of 4-Aryl-1,2,5,6-tetrahydropyrid-2-ones Using Potassium Permanganate

Oxidation of 4-phenyl-, 4-(4-pyridyl)-, and 4-phenethenyl-1,2,3,6-tetrahydropyridines with potassium permanganate can stop at the stage of the introduction of an oxo group into the allyl C₍₂₎ position of the piperideine fragment. In contrast to their precursors, 4-aryltetrahydropyridin-2-ones obtained in this way can be converted to 3,4-dihydroxy-2-oxopiperidines under Wagner reaction conditions.     

Studies on the constituents of Broussonetia species X. Six new alkaloids from Broussonetia kazinoki Sieb.

Six new alkaloids, broussonetines W, X, M1, U1, J3, and J2 (1-6) were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) as minor constituents. They were formulated as (2R,3R,4R,5R)-2-hydroxy-methyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyllpyrrolidine (1), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyl]pyrrolidine-4-O-beta-D-glucopyranoside (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(9R)-9,13-dihydroxytridecyl]- pyrrolidine (3), (2S,3S,4S)-2-hydroxymethyl-3,4-dihydroxy-5-(10-oxo-13-hydroxytridecyl)-5- pyrroline (4), (2R)-2-[(IS,2S)-1,2-dihydroxy-8-1(2R,3R,4R,5R)-5-(2-hydroxymethyl-3,4-dihydroxy-1-acetylpyrrolidinyl)loctyl]piperidine (5), (2R)-2-[(1S,2S)-1,2-dihydroxy-8-[(2R,3R, 4R,5R)-5-(2-hydroxymethy]-3,4-dihydroxypyrrolidinyl)]octyl]piperidine (6).     

Anti-isohumulone and its derivatives

Three new humulone derivatives have been isolated and identified as: 3,4-dihydroxy-2-(3-methyl-2-butenyl)-4-(4-methyl-3-pentenoyl)-2-cyclopentenone (6);4-ethanoyl-3,4-dihydroxy-2-(3-methyl-2-butenyl)-2-cyclopentenone (7) and 3,4-dihydroxy-2-(3-methyl-2-butenyl)-2-cyclopentenone (8), respectively. They arise by deacylation of anti-isohumulone (3_a), which is formed from humulone (1a) following an isomerization with ring contraction in opposite direction than the usual one producing isohumulones (2a).     

Efficient synthesis of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

An efficient synthesis of naturally occurring compounds isolated from Pentas longiflora, cis-3,4-dihydroxy-3,4-dihydromollugin 2, and trans-3,4-dihydroxy-3,4-dihydromollugin 3 is described. The O-protected mollugins were dihydroxylated using OsO4 to achieve the corresponding cis-dihydroxy derivatives in excellent yield. The synthesis of trans-3,4-dihydroxy-3,4-dihydromollugin was achieved using Oxone in good yield. A mechanism for the formation of cis-3,4-dihydroxymollugin acetonide from the reaction of mollugin with Oxone is proposed.     

Facile addition of methyl lithium to a 4-vinylpyridine system

The rapid addition of methyl lithium to the 4-vinylpyridine system present in 4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2-methyl-4-(4-pyridyl)but-3-en-2-ol ( 2 ) is reported. The α and β-4-{2,6-dihydroxy-4-(3-methyl-2-octyl)phenyl}-2,3-dimethyl-4-(4-pyridyl)butan-2-ols 4 and 5 formed, are cyclised by heating with 5N hydrochloric acid to trans and cis-3,4-dihydro-5-hydroxy-7-(3-methyl-2-octyl)-4-(4-pyridyl)-2,2,3-trimethyl-2H-1-benzopyran 6 and 7 respectively.     

Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

The first asymmetric synthesis of all four isomers of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

Asymmetric synthesis of all the four stereoisomers of cis-3,4-dihydroxy-3,4-dihydromollugins 4 and 6 and trans-3,4-dihydroxy-3,4-dihydromollugins 5 and 7 was achieved. The O-methoxymethyl mollugin derivatives were dihydroxylated to (−)- and (+)-cis-3,4-dihydroxy-3,4-dihydromollugin derivatives using both AD-mix-α and AD-mix-β. Deprotection of the MOM-ethers of cis-dihydroxy compounds resulted in the targeted stereoisomers (−)-(3R,4R)-cis-3,4-dihydroxy-3,4-dihydromollugin 4, (−)-(3R,4S)-trans-3,4-dihydroxy-3,4-dihydromollugin 5, (+)-(3S,4S)-cis-3,4-dihydroxy-3,4-dihydromollugin 6 and (+)-(3S,4R)-trans-3,4-dihydroxy-3,4-dihydromollugin 7. These routes were paved with difficulties, for example, incompatibility of the substrates with AD-mixes, the unexpected formation of trans-dihydroxy compounds and failures in deprotection protocols.     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Tetracarbonyl Systems: VII. Reactions of 1,3,4,6-Tetracarbonyl Compounds with o-Aminothiophenol in the Synthesis of Regioisomeric 3(2)-Aroylmethylene-1,4-benzothiazin-2(3)ones

In reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with o-aminothiophenol (3Z)-3-aroylmethylene-3,4-dihydro-2H-1,4-benzothiazin-2-ones were obtained in a preparative yield. In solution of the latter compounds an enamine-imine tautomerism was observed. In reaction of ethyl esters or amides of 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acids with the o-aminothiophenol regioisomeric 2-aroylmethylene-2H-1,4-benzothiazin-3(4H)-ones were formed.     

1,3,4,6-Tetracarbonyl Compounds: VI. Synthesis of 2-Substituted 6-Aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic Acid Esters and Amides

The Knoevenagel reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with ethyl cyanoacetate or malonodinitrile yields 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters or amides which exhibit biological activity. The structure of the products is discussed, taking into account the structure of known 3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters and 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones.     

Stereochemistry of the hydrocyanation of hydroxypiperidin-4-ones

Preparative methods have been developed for the preparation of stereoisomers of 3,4-dihydroxy-1,3-dimethyl-6-(4-chlorophenyl)-4-cyanopiperidin-4-ones. Products with the cyano group equatorial predominate in the equilibrium mixtures of the cyanohydrins synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–676, May, 1993.     

Two new pyrrolidine alkaloids, radicamines A and B, as inhibitors of alpha-glucosidase from Lobelia chinensis Lour

Two new pyrrolidine alkaloids, radicamines A and B were isolated as inhibitors of alpha-glucosidase from Lobelia chinensis Lour. (Campanulaceae). Radicamines A and B were formulated as (2S,3S,4S,5S)-2-hydroxymethyl-3,4-dihydroxy-5-(3-hydroxy-4-methoxyphenyl)-pyrrolidine (1) and (2S,3S,4S,5S)-2-hydroxymethyl-3,4-dihydroxy-5-(4-hydroxyphenyl)-pyrrolidine (2) on the basis of spectroscopic analyses and chemical methods.     

Chemical constituents from Piper marginatum Jacq. (Piperaceae)—antifungal activities and kinetic resolution of (RS)-marginatumol by Candida antarctica lipase (Novozym 435)

The leaves of Piper marginatum contain the antifungal compounds 3,4-methylenedioxypropiophenone 1, 2-methoxy-4,5-methylenedioxypropiophenone 2, 1-(3,4-methylenedioxyphenyl)propan-1-ol 3 (marginatumol), 5,4′-dihydroxy-7-methoxyflavanone 4 and 5,7-dihydroxy-4′-methoxyflavanone 5. The absolute configuration of natural marginatumol was determined as (+)-(R)-3 (ee 48%) by comparison of its optical properties with the chiral forms obtained by kinetic resolution of racemic 3 using Candida antarctica lipase (Novozym 435).     

Synthetic approaches to imino sugar (2R,3R,4S)-2-(hydroxymethyl)-4-methylpyrrolidine-3,4-diol from naturally occurring sugar and amino acid

Imino sugar compound 3 was prepared by two alternative routes starting from ribose and d-serine. From d-serine (3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methylpyrrolidin-2-one was prepared in five steps in 50% overall yield, which was further converted into (2R,3R,4S)-2-(hydroxymethyl)-4-methylpyrrolidine-3,4-diol in three steps in 23% overall yield.     

Isofagomine lactams,synthesis and enzyme inhibition

The synthesis of isofagomine lactams (2-oxoisofagomines) corresponding to the biologically important hexoses is presented. The D-glucose/D-mannose analogue (3S,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (9) was synthesised in 9 steps from D-arabinose, the D-galactose analogue (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (10) was synthesised in 11 steps from D-arabinose and the L-fucose analogue (3R,4R,5R)-3,4-dihydroxy-5-methylpiperidin-2-one (11) was synthesised in 12 steps from L-arabinose. The three lactams 9-11 were found to be glycosidase inhibitors with micro- to nanomolar inhibition constants. The lactam 10 showed slow onset inhibition of beta-galactosidase from A. Oryzae. The rate constants for this process were determined to be k(on) = 2.55 x 10(4) M-1 s-1 and k(off) = 1.7 x 10(-3) s-1. The activation energies and standard thermodynamic functions were also determined.     

Synthesis of robustin and related 4-hydroxy-3-phenyl coumarins and isoflavones

Robustin (31a) occurring in the roots of Derris robusta has been synthesised from mono-O-methylphloroglucinol (20) as follows. Hoesch condensation with homopiperonitrile (21) gave 2,4-dihydroxy-6-methoxyphenyl 3,4-methylenedioxybenzyl ketone (22) which on reaction with 2-hydroxy-2-methyl-3-butene in the presence of borontrifluoride-etherate afforded 5-C-(24) and 3-C-(23) prenyl derivatives. These on cyclodehydrogenation with DDQ followed by coumarin condensation with ethyl chloroformate yielded robustin (31a) and isorobustin (32) respectively. Model experiments with nuclear prenylation of 2,4-dihydroxy-6-methoxy-phenyl benzyl ketone (1), followed by oxidative cyclisation and either courmarin or isoflavone condensation have yielded new isopentenylated 4-hydroxy-3-phenylcourarins or isoflavones.     

Thermal analyses and spectral characterization of some synthesized metal(II) Schiff base complexes

Schiff base metal complexes derived from 2-thiophenecarboxylidine-4-anisidine, 3,4-dihydroxy-5-nitrobenzylidine-2-amino-5-methylthiazole and 3,4-dihydroxy-5-nitrobenzylidine-4-chloroaniline have been synthesized and characterized by elemental analysis, IR, UV?CVis, molar conductance and thermal analyses. The complexes are coloured and stable in air at room temperature. The complexes exhibit coordination number to be 4 and 6. The thermal behaviour of metal complexes shows that the hydrated complexes lose water molecules of hydration in the first and then is immediately followed by decomposition of ligand molecules in the subsequent steps.     

Simple procedure for preparation of quinoxalin-2(1H)-one 3-[Oxo(cyclo)alkyl(idene)] derivatives

A simple preparative procedure was developed for 3-(2-oxoalkylidene)-3,4-dihydroquinoxalin-2(1H)-ones, 4,5-dihydroxy-1-[3-oxo-3,4-dihydroquinoxalin-2(1H)-ylidene]-3,5-octadiene-2,7-dione, and 3-(2,3-dihydroxy-4-methyl-5-oxo-1,3-cyclopentadien-1-yl)quinoxalin-2(1H)-one by reaction of methyl ketones first with diethyl oxalate in the presence of sodium, and then with o-phenylenediamine.     

Two new compounds from Dendrobium candidum

Two new compounds were isolated from the stems of Dendrobium candidum: (R)-3,4-dihydroxy-5,4',alpha-trimethoxybibenzyl (1), named dendrocandin A; and 4-[2-[(2S,3S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-2-hydroxymethyl-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl]ethyl]-1-methoxyl benzene (2), dendrocandin B. Five previously known bibenzyls were also identified: 4,4'-dihydroxy-3,5-dimethoxybibenzyl (3), 3,4-dihydroxy-5,4'-dimethoxybibenzyl (4), 3-O-methylgigantol (5), dendrophenol (6), and gigantol (7).     

Xanthones from stems of Hypericum chinense

Six new xanthones, 4,6-dihydroxy-2,3-dimethoxyxanthone (1), 2,6-dihydroxy-3,4-dimethoxyxanthone (2), 6-hydroxy-2,3,4-trimethoxyxanthone (3), 3,6-dihydroxy-1,2-dimethoxyxanthone (4), 4,7-dihydroxy-2,3-dimethoxyxanthone (5), and 3,7-dihydroxy-2,4-dimethoxyxanthone (6) were isolated from the stems of Hypericum chinense, together with four known xanthones. Their structures were established based on spectroscopic studies.