HETEROCYCLES

■ Preparation of D-Cycloserine and 13C-Labeled D-Cycloserine

Nathan C. Thacker, Judit Molnár-Tóth, Judy L. Miska, Raul G. Barletta, and James M. Takacs*

*Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, U.S.A.

■ PHOSPHONIUM CHLORIDE AS A NON-VOLATILE CHLORINATING REAGENT: PREPARATION AND REACTION IN NO SOLVENT OR IONIC LIQUID

Osamu Sugimoto,* Yukihiro Harada, and Ken-ichi Tanji*

*Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

Reaction of triphenylphosphine with trichloroisocyanuric acid in no solvent or an ionic liquid gave the corresponding phosphonium chloride, which can be used as a cheap and safe chlorinating reagent. Conversion of hydroxyheterocycles to chloroheterocycles, carboxylic acids to carboxylic acid chlorides, and primary amides to nitriles were accomplished by using the phosphonium chloride in excellent to good yields.

■ A NEW GALLOYLBERGENIN FROM BERGENIA cRASSIFOLIA WITH ANTI-LIPID DROPLET ACCUMULATION ACTIVITY

Jenis Janar, Liang Fang, Chin Piow Wong, Toshio Kaneda, Yusuke Hirasawa, Burasheva Gauhar Shahmanovna, Abilov Zharylkasyn Abduahitovich, and Hiroshi Morita*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

A new bergenin derivative, 3,11-di-O-galloylbergenin (1) was isolated from the roots of Bergenia crassifolia together with four known related compounds. Their structures were elucidated by spectroscopic and chemical analysis. The new galloylbergenin showed a moderate anti-lipid droplet accumulation activity.

■ BIOMIMETIC SYNTHESIS OF CHROBISIAMONE A FROM CASSIA sIAMEA

Yuichiro Tomizawa, Jun Deguchi, Tokio Ishikawa, Toshio Honda, and Hiroshi Morita*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Chrobisiamone A (1), an unique chromone dimer from leaves of Cassia siamea Lam. (Leguminosae), was synthesized from 5-acetonyl-7-hydroxy-2-methylchromone (2) in 4 steps through biomimetic Michael addition.

■ NEW INDOLE ALKALOIDS FROM ALSTONIA MACROPHYLLA

Jun Deguchi, Tomokazu Shoji, Yusuke Hirasawa, Abdul Rahman, Osamu Shirota, and Hiroshi Morita*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Alkaloidal investigations of Alstonia macrophylla led to the isolation of a new 3-alkylpyridinium-indole-2-carboxylate scaffold alkaloid, N(1)-demethyl-7-methoxyikirydinium A (1) and a yohimbane-type alkaloid, 10-methoxydihydrosempervirine (2), and two strychane-type alkaloids, 17-carboxylcompactivervine N-oxide (3) and 17-carboxylalstovine N-oxide (4). Their structures were elucidated by NMR spectral analysis using 2D techniques and CD spectra.

■ NEW ASPIDOFRACTININE, ASPIDOSPERMATAN AND AKUAMILINE INDOLE ALKALOIDS FROM THE ROOTS OF KOPSIA SINGAPURENSIS RIDL.

Kartini Ahmad, Yusuke Hirasawa, Alfarius Eko Nugroho, A. Hamid A. Hadi, and Hiroshi Morita*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Three new aspidofractinine; N(1)-formylkopsininic acid (1), N(1)-formylkopsininic acid-N(4)-oxide (2), 15-hydroxykopsamine (3), a new aspidospermatan; 14α-hydroxy-N(4)-methylcondylocarpine (4), and a new akuamiline; singaporentinidine (5) type indole alkaloids were isolated from the roots of Kopsia singapurensis. Their structures were determined on the basis of the 2D NMR and chemical correlations.

■ SYNTHESIS OF 1,4-PHOSPHASILACYCLOHEXA-2,5-DIENES BEARING HYDROGEN OR CHLORINE ATOMS ON THE SILICON ATOMS

Yoshiyuki Mizuhata, Satoshi Morikawa, and Norihiro Tokitoh*

*Division of Synthetic Chemistry, Organoelement Chemistry, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

Abstract

2,3,5,6-Hydrogen-substituted 1,4-phosphasilacyclo¬hexa-2,5-dienes bearing a functional group on the silicon atom were synthesized via the corresponding stannacycle. The structures of newly synthesized silacyclic compounds were determined by X-ray crystallographic analysis.

■ SYNTHESIS AND STABILITY OF 3-HYDROXYANAGRELIDE, A BIOLOGICALLY POTENT METABOLITE OF ANAGRELIDE

Richard B. Scott, Kristin M. Downey, Keith P. Healy, Alistair P. Henderson, Claire L. Robinson, William Clegg, Ross W. Harrington, Richard Franklin, and Bernard T. Golding*

*School of Chemistry, Newcastle University, Bedson Building, NE1 7RU, U.K.

Abstract

Human metabolism of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2-one (anagrelide), a drug used for the treatment of essential thrombocythemia, gives 6,7-dichloro-3-hydroxy-1,5-dihydroimidazo[2,1-b]quinazolin-2-one (3-hydroxyanagrelide) and 2-amino-5,6-dichloro-3,4-dihydroquinazoline. To enable the chemical and biological properties of 3-hydroxyanagrelide to be fully evaluated, a synthetic route to the racemic compound has been developed. In an aqueous buffer (pH 7.4, 37 ºC) 3-hydroxyanagrelide readily equilibrates with an isomer, 6,7-dichloro-1-hydroxy-3,5-dihydro-imidazo[1,2-a]quinazolin-2-one, and is also hydrolyzed to 2-amino-5,6-dichloro-3,4-dihydroquinazoline. 3-Hydroxyanagrelide (half-life 40 hours) was the dominant species at equilibrium and it was concluded that the equilibration and decomposition are sufficiently slow that published assays of 3-hydroxyanagrelide are reliable.

■ CATALYTIC ASYMMETRIC INTERMOLECULAR C–H INSERTION OF 1,4-CYCLOHEXADIENE WITH α-ALKYL-α-DIAZOESTERS USING CHIRAL DIRHODIUM(II) CARBOXYLATES

Takayuki Goto, Tomohiro Onozuka, Yuhei Kosaka, Masahiro Anada, Koji Takeda, and Shunichi Hashimoto*

*Laboratory of Synthetic and Industrial Chemistry, Graduate School of Life Science, Division of Life Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

The first example of dirhodium(II) complex-catalyzed asymmetric intermolecular C–H insertion with α-alkyl-α-diazoesters is described. The reaction of 1,4-cyclohexadiene with 2,4-dimethyl-3-pentyl α-alkyl-α-diazoacetates under catalysis by dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, or dirhodium(II) tetrakis[N-tetrafluorophthaloyl-(S)-tert-leucinate], Rh2(S-TFPTTL)4, gave the corresponding C–H insertion products with enantioselectivities of up to 86% ee, albeit in low to modest yields.

■ Synthesis of a Library of 1,5,2-Dithiazepine 1,1-Dioxides. Part 1: A One-Pot Sulfonylation/Thia-Michael Protocol

Qin Zang, Aihua Zhou, Salim Javed, Pradip K. Maity, Chirs A. Knudtson, Danse Bi, Jared J. Hastings, Fatima Z. Basha, and Paul R. Hanson*

*5029 Malott Hall, Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr., Lawrence
Kansas 66045-7582, U.S.A.

Abstract

A novel one-pot sulfonylation/intramolecular thia-Michael protocol is reported for the synthesis of 1,5,2-dithiazepine 1,1-dioxides. Sulfonylation between cysteine ethyl ester/cysteamine and 2-chloroethanesulfonyl chloride, followed by in situ intramolecular thia-Michael addition, was achieved and afforded the titled 1,5,2-dithiazepine-1,1-dioxide scaffolds. Diversification was demonstrated for future library synthesis.

■ SYNTHESIS OF A LIBRARY OF 1,5,2-DITHIAZAPINE 1,1-DIOXIDES. PART 2: ROUTES TO BICYCLIC SULTAMS

Qin Zang, Salim Javed, Aihua Zhou, Chirs A. Knudtson, Danse Bi, Fatima Z. Basha, and Paul R. Hanson*

*Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr., 66045-7582, U.S.A.

Abstract

The synthesis of a library of bicyclic sultams incorporating the 1,5,2-dithiazepine-1,1-dioxide moiety is reported. Following scaffold synthesis via a one-pot sulfonylation/intramolecular thia-Michael (“cy-click”) protocol, several additional cyclization strategies have been realized enabling access to new bicyclic sultams.

■ Formal Synthesis of (±)-Clausenamide by NHC-Catalyzed γ-Lactam Formation

Ming He, Michael Rommel, and Jeffrey W. Bode*

*Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zuerich, Switzerland

Abstract

(±)-Clausenamide is a biologically active γ-lactam isolated as a racemic mixture from Clausena lansium. Reported medicinal properties include hepatoprotective effects as well as neuroprotective and nootropic activity. In order to improve synthetic access to this molecule and its analogues, and to devise a route amenable to asymmetric catalysis, we have developed a new formal synthesis of (±)-clausenamide based on an N-heterocyclic carbene (NHC) catalyzed annulation of cinnamaldehyde and an unsaturated imine. The key γ-lactam forming annulation proceeds at room temperature in good yield and excellent diastereoselectivity. Preliminary efforts towards an enantioselective variant are also reported.