Regular Issue

Vol. 27, No. 8, 1988

22 data found. 1 - 22 listed
Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1803 - 1807
Published online:
DOI: 10.3987/COM-88-4536
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


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1809 - 1812
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DOI: 10.3987/COM-88-4548
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


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1813 - 1816
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DOI: 10.3987/COM-88-4566
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.


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1817 - 1820
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DOI: 10.3987/COM-88-4589
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.


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1821 - 1825
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DOI: 10.3987/COM-88-4604
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.


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1827 - 1836
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DOI: 10.3987/COM-88-4609
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


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1837 - 1843
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DOI: 10.3987/COM-88-4610
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


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1845 - 1853
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DOI: 10.3987/COM-88-4611
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


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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Communication | Regular issue | Vol 27, No. 8, 1988, pp. 1855 - 1860
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DOI: 10.3987/COM-88-4616
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1861 - 1866
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DOI: 10.3987/COM-87-4432
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1867 - 1871
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DOI: 10.3987/COM-88-4530
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.


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1873 - 1879
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DOI: 10.3987/COM-88-4547
Actinocinyl-bis(hemin); DNA-Intercalating Cleavage Agent

Yushin Nakamura*

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1881 - 1885
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DOI: 10.3987/COM-88-4553
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1887 - 1897
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DOI: 10.3987/COM-88-4562
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1899 - 1905
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DOI: 10.3987/COM-88-4581
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1907 - 1923
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DOI: 10.3987/COM-88-4594
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1925 - 1928
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DOI: 10.3987/COM-88-4597
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.


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1929 - 1933
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DOI: 10.3987/COM-88-4598
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.


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1935 - 1944
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DOI: 10.3987/COM-88-4602
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


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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Paper | Regular issue | Vol 27, No. 8, 1988, pp. 1945 - 1952
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DOI: 10.3987/COM-88-4615
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


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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Review | Regular issue | Vol 27, No. 8, 1988, pp. 1953 - 1973
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DOI: 10.3987/REV-88-387
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


The utilities of thioamide groups as synthetic intermediates to heterocycles are presented.

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Review | Regular issue | Vol 27, No. 8, 1988, pp. 1975 - 2003
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DOI: 10.3987/REV-88-391

Alba Chimirri, Silvana Grasso, Giovanni Romeo, and Maria Zappalã

*Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy


This review describes the synthesis, the reactivity, the spectroscopic data and the biological activities of thiazolo-benzimidazoles.

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22 data found. 1 - 22 listed