HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 27, No. 8, 1988
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■ Fluoroazoles. An MNDO SCF MO Study
Jordi Garcia and Jaume Vilarrasa*
*Departmento de Química Orgánica, Instituto Químico de Sarriá, Universitat de Barcelona, 08028 Barcelona, Spain
Abstract
MNDO calculations are reported for 43 fluorine-containing nitrogenated five-membered rings. The available experimental data, on fluoropyrazoles 10-15 and other fluoroazoles, correlate quite well with the calculatetl energies and charge distributions. In the light of such results, some properties of interesting fluoroazoles not yet synthesized may be predicted.
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■ Languiduline, a Diterpenoid with an Unusual Structure from Salvia languidula
Jorge Cárdenas,* Baldomero Esquivel, Rubén A. Toscano, and Lydia Rodríguez-Hahm
*Facultad de Química, Universidad Nacional Autónama de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510, Mexico
Abstract
The unusual structure of languiduline, a new diterpenoid isolated from Salvia languidula Epl (Labiatae), was deduced from the spectral data and confirmed by X-ray diffraction analysis.
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■ Structure and Stereochemistry of Thalicsiline, a New Antiinflammatory C20 — Diterpenoid Alkaloid from Thalictrum sessile
Yang-Chang Wu,* Tian-Shung Wu, Masatake Niwa, Sheng-Teh Lu, Yoshimasa Hirata, Donald R. McPhail, Andrew T. McPhail,* and Kuo-Hsiung Lee*
*Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, U.S.A.
Abstract
Antiinflammatory thalicsiline, the first ajaconine-type alkaloid bearing an oxygen funcrton at C6, has been isolated from Thalictrum sessile, and its structure and stereochemistry have been established by spectral data and a single-crystal-X-ray analysis.
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■ 3-O-(1-Phenyltetrazol-5-yl)morphine in the Acid-catalyzed Morphine-Apomorphine Rrearrangement: Formation of a Side Product Due to 1-Phenyltetrazole Group Migration
Prem Mohan* and Joseph G. Cannon
*Department of Medical Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, P.O.Box 6998, Chicago, IL 60680, U.S.A.
Abstract
Acid catalyzed rearrangement of the title compound leads to a second aporphine derivative in addition to the expected product, 10-O-(1-phenyltetrazol-5-yl)-apomorphine. This side product is isomeric with the expected product, and it was shown to be 11-O-(1- phenyltetrazol-5-yl)apomorphine, apparently formed by tetrazole ring migration in the course of the acid catalyzed rearrangement of the morphine derivative.
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■ Syntheses and Flash Vacuum Pyrolyses of Highly Functionalized α-N-Hydroxy Amino Acids
Nai Zhong Huang, and Marvin J. Miller*
*Department of Chemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Abstract
Flash vacuum pyrolysis (FVP) of N-acetoxy-N-vinyacetylmethionine sulfoxide and N-acetyl-N-hexadienoylglycine produced dihydropyridones, presumably by cycloaddition reactions of intermediate imines.
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■ Flavine Coenzyme Mediated Photooxidation of 3’,4’-Anhydrovinblastine. Further Information on the Later Stages of Bisindole Alkaloid Biosynthesis.
James Peter Kutney,* Lewis Siu Leung Choi, Jun Nakano, and Hiroki Tsukamoto
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Flavine coenzyme mediated photooxidation of 3’,4’-anhydrovinblastine (4) has afforded an excellent route to the highly unstable dihydropyridinium intermediate 3. The role of 3 as the initially formed biointermediate in the enzyme-catalyzed coupling of catharanthine (1) and vindoline (2) can now be evaluated in terms of irs crucial role in the biosynthesis of the various bisindole alkaloids such as 4, leurosine (5). catharine (6). vinblastine (7). and vinamidine (8). Extensive studies are presented to establish the structure and chemistry of 3. Techniques such as 13C-nmr and Attached Proton Test (APT) are employed. It is also shown that in the non-enzymatic FMN conversion of 4 to 3, the process proceeds with preferential removal of the C5’-αH in the indole unit of 4 (66% removal in deuterio-labelled as substrate) while in the comparable enzymatic conversion predominant retention of this proton is maintained (65% retention of C5’-αH in deuterio-labelled 4). A similar study in the bioconversion of 4 to 3 with commercial horseradish peroxidase reveals a 50% removal of this proton. Clearly the nature of the stereoselectivicy of the enzymatic process in the generation of 3 is dependent on the nature of oxidases/peroxidases present in the enzyme mixture employed. These studies also provide mechanistic information about the one-electron promoted bioconversion of 4 to 3.
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■ Biomimetic Chemical Transformation of 3’,4’-Anhydrovinblastine to Vinblastine and Related Bisindole Alkaloids
James Peter Kutney,* Lewis Siu Leung Choi, Jun Nakano, and Hiroki Tsukamoto
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Employing flavine co-enzyme mediated photooxidation and reduced nicotinamide-adenine dinucleotide (β-NADH) as reactant, 3’,4’-anhydrovinblastine (4) is transformed into vinblastina (5), 4’-deoxyleurosidins (14), vinamidine (8) and its reduction product (16). In this biomimetic transformation of 4 to the end products, unstable intermediates are recognized and their structures established by appropriate deuterium labelled experiments. The results obtained provide important information on the nature of biointermediates involved in the later stages of the biosynthetic pathway of vinblastine and related bisindols alkaloids. Contrary to earlier speculations proposed from various laboratories. 4 is not a biosynthetic precursor for the above-mentioned alkaloids. Its formation is the result of regiospecific 1,2-reduction of the true biosynthetic precursor, the highly unstable dihydropyridinium intermediate 3. The latter, after enzymatically controlled conversion to 10, 11 and 12, then affords routes to the alkaloids 5,8 and 14.
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■ A Highly Efficient and Commercially Important Synthesis of the Antitumor Catharanthus Alkaloids Vinblastine and Leurosidine from Catharanthine and Vindoline
James Peter Kutney,* Lewis Siu Leung Choi, Jun Nakano, Hiroki Tsukamoto, Michael McHugh, and Camille Andre Boulet
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Extensive studies of various reaction parameters for the chemical coupling of catharanthine (1) and vindoline (2) followed by evaluation of highly unstable intermediates by careful reaction control have provided essentially a quantitative yiald in this coupling reaction. Subsequent regioselective reduction of the resultant intermediate 3 by select NADH models affords. a high yield of an enamins (5) which, without isolation, is selectively oxidized to unstable iminium intermediates 6 and 7 and the latter, again without isolation. are finally reduced to vinblastins (8,40%), leurosidine (10,16%), and 3’,4’-enhydrovinblastine (4,12%). The entire process of five steps (1→11+2→3→5→6,7→8,10,4) can be achieved in a one-pot operation and the high overall yield of vinblastine (8) requires that each reaction must proceed in yields in excess of 80%.
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■ The Friedel-Crafts Acylation of Ethyl Pyrrole-2-carboxylate. Scope, Limitations, and Application to Synthesis of 7-Substituted Indoles
Yasuoki Murakami,* Masanobu Tani, Takahiro Ariyasu, Chika Nishiyama, Toshiko Watanabe, and Yuusaku Yokoyama
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
The Friedel-Crafts acylation of ethyl pyrrole-2-carboxylate (3) was studied under a variety of conditions using various Lewis acids and acyl chlorides. The acylation with some Lewis acids such as BF3 OEt2 gave a mixture of 4- and 5-acyl derivatives (5 and 6), whereas the acylation with various acyl chlorides in the presence of AlCl3 gave exclusively 4-acyl derivatives (5). Acylation in this experiment was applied to a new methodology for synthesis of 7-substituted indoles.
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■ Reactions with Heterocyclic Enaminonitriles: Synthesis of Pyrrolo[2,3-b]pyridine, Pyrrolo[2,3-d]pyrimidine and Pyrrole Derivatives
Abdou O. Abdelhamid,* Fathy M. Abdel-Galil, and Sohair S. Saleh
*Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
Abstract
Synthesis of pyrrolo[2,3-b]pyridine, pyrrolo[2,3-d]pyrimidine and pyrrole derivatives utilizing 1-ary1-2-amino-3-cyano-5-ethoxycarbonyl-4-methylpyrrole derivatives 2 as starting components is reported.
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■ Synthesis of 2-Alkylpyrimidines via 2-Alkyl-1,4,5,6-tetrahydropyrimidines
Richard Garth Pews*
*Organic Specialties Laboratory, Central Research, The Dow Chemical Company, 1776 Building, Midland, Michigan 48674, U.S.A.
Abstract
The condensation of 1,3-diaminopropane with alkanoic acids gives 2-alkyl-1,4,5,6-tetrahydropyrimidines. Dehydrogenation of the tetrahydropyrimidine derivatives over a palladium catalyst produces the 2-alkylpyrimidines in high yields.
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■ Actinocinyl-bis(hemin); DNA-Intercalating Cleavage Agent
Yushin Nakamura*
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Abstract
The synthesis of actinocinyl-bis(mesoporphyrinatoiron) (1) was described. The intercalating bis(hemin) (1) caused effective DNA scission in the presence of Na2S2O4 under air.
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■ Synthesis of New Uraciles Having N-Amino-β-,γ- and δ-lactams
Tadashi Okawara, Toshifumi Shono, Tetsuo Yamasaki, and Mitsuru Fiurukawa*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
The reaction of 1,3-dimethyl-6-methylhydrazinouracil 1 with various haloacyl halides 2 afforded N-haloacylhydrazinouraciles 3, which were converted into the corresponding lactams 4 by treatment with KOH in the presence of BTEAC.
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■ Tropane Alkaloids from Schizanthus pinnatus
Gabriel de la Fuente,* Matías Reina, Orlando Muñoz, Aurelio San Martín, and Jean-Pierre Girault
*Centro de Productos Naturales Orgánicos "Antonio González", Universidad de La Laguna, Avda. Astrofísico Franciso Sánchez, 2, 38206- La Laguna, Tenerife, Spain
Abstract
From Schizanthus pinnatus Ruiz et Pav. we have isolated seven new tropon-3α,6β-diol diesters, schizanthines F (1), G (2), H (3), I (4), K (8), L (9), and M (10), together with tropine, (-)-6β-angeloyloxytropan-3α-ol (5), (-)-6β-tigloyloxytropan -3α-ol (6), and (-)-3α-senecioyloxytropan-6β-ol (7). The structures of the new alkaloids were determined mainly by spectroscopic methods comprising 2-D and 1-D nmr long-range heteronuclear correlations.
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■ Photochemical Rearrangements of 3-Methylisoxazolopyridines
Donato Donati, Stefania Fusi, Fabio Ponticelli,* and Piero Tedeschi
*Istituto di Chimica Organica, Università di Siena, Pian dei Mantellini 44, 53100 Siena, Italy
Abstract
Irradiation in water.-saturated ehyl ether of isoxazolopyridines 1a,e, beside the corresponding oxazolopyridines 2a,e, leads to N-methylcarboxamides 3a,e via 1-2 shift of the methyl group. The lsoxazolopyridine 5, bearing a hydrazino group in 4-position, rearranges only to 1-aminopyrazolopyridine 6.
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■ 2(3H)- and 2(5H)-Furanones. III. An Efficient Synthesis and the Eschenmoser-Mannich Reaction of N-Substituted 4-Amino-2(5H)-furanones
Takefumi Momose,* Naoki Toyooka, Takafumi Nishi, and Yumi Takeuchi
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
A series of N-substituted 4-amino-2(5H)-furanones (II) was derived from β-tetronic acid (I) by direct action of several aliphatic and aromatic amines. The Eschenmoser-Mannich reaction of II readily gave the corresponding Mannich bases (VI) quantitatively.
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■ Diels-Alder Reactions of 6-Azapterins. An Alternative Strategy for the Synthesis of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid (DDATHF)
Edward C. Taylor,* Philip M. Harrington, and John C. Warner
*Department of Chemistry, Princeton University , Princeton, New Jersey 08544, U.S.A.
Abstract
Methyl 2-N-pivaloyl-5,10-dideazapteroate (7), a key intermediate in our recent unambiguous synthesis of the new antitumor agent, 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), has been synthesized by a novel inverse electron demand Diels-Alder reaction between 2-N-pivaloyl-7-methylthio-6-azapterin (4) and the pyrrolidine enamine of methyl p-(4-oxobutyl) benzoate, followed by Raney nickel desulfurization of the resulting 7-methylthio derivative (5).
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■ Cycloaddition of Isopropylidene Mehtylenemalonate to Isosafrole and Analogues
Robert Stevenson* and James V. Weber
*Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454-9110, U.S.A.
Abstract
Isopropylidene methylenemalonate (methylene Meldrum’s acid) serves as a heterodiene, rather than dienophile in 1:1 adduct formation at room temperature with isosafrole, styrene and p-methoxystyrene The resultant aryltrioxabicyclo[4.4.0]decl(6)-en-5-one heterocyclic products are degraded under mild hydrolytic conditions to yield the corresponding δ-aryl-δ-valerolactone or 5-arylpent-4-enoic acid.
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■ Iminophosphorane-mediated Synthesis of Fused [1,3,4] Thiadiazoles: Preparation of Imidazo[2,1-b][1,3,4]thiadiazoles and [1,3,4]Thiadiazolo[2,3-c][1,2,4]triazine Derivatives
Pedro Molina,* Angeles Lorenzo, Ma Jesús Vilaplana, Enrique Aller and José Planes
*Departmento de Química Orgánica, Facultad de Ciencias, Universidad de Murcia, 30071 Murcia, Spain
Abstract
A number of fused [1,3,4]thiadiazoles 4 and 7 - have been prepared by treatment of iminophosphoranes 2 and 6 wth acyl chlorides under neutral conditions.
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■ Efficient Synthesis of Oligo-N-methylpyrrolecarboxamides and Relateed Compounds
Eiji Nishiwaki, Shigeaki Tanaka, Hideaki Lee, and Masayuki Shibuya*
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi 1, Tokushima 770-8505, Japan
Abstract
1-Methyl-4-nitro-2-trichloroacetylpyrrole 5, a new precursor for the syntheses of oligo-N-methylpyrrolecarboxamide antibiotics and their analogues, was prepared with facility. The versatility of 2 was demonstrated by the syntheses of oligopeptides 16-19. 1-Methyl-4-nitro-2-trichloroacetylimidazole 8 was also prepared for a precursor of oligo-N-methylimidaezolecarboxamidds.
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■ Synthesis of Heterocycles Using Thioamide Groups
Hiroki Takahata* and Takao Yamazaki*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
The utilities of thioamide groups as synthetic intermediates to heterocycles are presented.
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■ Thiazolobenzimidazoles
Alba Chimirri, Silvana Grasso, Giovanni Romeo, and Maria Zappalã
*Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy
Abstract
This review describes the synthesis, the reactivity, the spectroscopic data and the biological activities of thiazolo-benzimidazoles.