HETEROCYCLES

■ Studies Directed toward the Total Synthesis of Perhydrohistrionicotoxin

E. J. Corey* and Richard D. Balanson

*Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachysetts 02138, U.S.A.

Abstract

Variations on a new synthetic approach to perhydrohistrionicotoxin (2) are described.

■ 8-α-Amido-5-azanonam-1,3-dienes Potential β-Lactam Antibiotics

Jacques Streith and Gérard Wolff*

*Ecole Nationale Supérieure de Chimie de Mulhouse, Université du Haut-Rhin, 68093 Mulhouse, France

Abstract

1,2-Diazepines 2 react stereospecifically with phtalimidoacetyl chloride in the presence of base to give the corresponding diazepino-β-lactams in high yield. Treatment of such an azetidinone (5) with sodium hydroxide and then with dicyclohexylcarbodiimide gave isoimide 7 which hydrolysed easily yo the corresponding 8-amino-5-azanonam-1,3-diene 8 in high overall yield. Acylation gave the 5-azanonam-1,3-dienes 9 which are the immediate precursors of the cephalosporin analogues 1.

■ Lipophilic Cryptates; Salt Solubilization and Anion Activation

Denis Clement, François Damm, and Jean-Marie Lehn*

*Institut Le Bel, Université Louis Pasteur, 4 Rue Blaise Pascal, 67070 Strasbourg, France

Abstract

Lipophilic cryptands (I) - (III) bearing C₁₀H₂₁ side chains have been studied. [2.2.2, C₁₀] (I) forms complexes with various metal cations and solubilizes salts in solvents of low polarity to a greater extent than the parent system. Solvation of F^- by one CHCl₃ molecule has been observed and is necessary for KF dissolution in benzene. A study of the basicity of the ter-AmO^- anion in the presence of cryptate counterions gave pK_a > 37 for ter-AmOH, a value approaching the gas phase properties.

■ The Structure of Harrisonin

Isao Kubo,* Steven P. Tanis, Yue-Wei Lee, Iwao Miura, Koji Nakanishi, and Andrew Chapya

*Department of Chemistry, Columbia University, 3000 Broadway, Mail Code 3114 New York, New York 10027, U.S.A.

Abstract

In the following we forward structure 1 for harrisonin isolated from the root bark of an East African shrub. Harrisonin has insect antifeeding, cytotoxic and antibacterial properties.

■ Steroids Having Sulfur-substituent Groups

Ken’ichi Takeda*

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

Abstract

A study was made of various methods for introducing a sulfur function into a steroid for the purpose of synthesizing cortisol having its 11β-hydroxyl replaced by a thiol group. While our efforts failed to yield the target compound, introduction of the sulfur function led to some interesting observations which we would like to report here.

■ Biosynthetic Studies with ¹³C Labeled Precursors

Urs Séquin and A. Ian Scott*

*Sterling Chemistry Laboratory, Yale University, 225 Prospect St., New Haven, CT 06511, U.S.A.

Abstract

Carbon-13 double labeling experiments are now widely used in the investigation of biosynthesis.

■ Total Synthesis of 2,4-Dioxyquinoline Alkaloids

Lester A. Mitscher,* Toshio Suzuki, George Clark, and Mohindar S. Bathala

*Department of Medicinal Chemistry, University of Kansas, 4070 Malott Hall, Lawrence, Kansas 66045-2506, U.S.A.

Abstract

The various total syntheses available for this wide-spread alkaloid family are reviewed.

■ Electrocyclic Reactions of Some Penta-1,4-diene Systems

Charles W. Shoppee*

*Department of Chemistry, University of Sydney, Sydney, N. S. W., Australia

Abstract

A review of some thermal ground state and photochemical excited state reactions involving electrocyclisation of cations and anions derived from 1,5-diphenylpenta-l,4-diene systems.

■ The Present Status of Malaria Chemotherapy

Arnoled Brossi*

*PV-C 65/403, Pharma Research, F.Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4002 Basel, Switzerland

■ Racemisation and Epimerisation in Isoquinoline and Indole Alkaloids

Tetsji Kametani* and Masataka Ihara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Stereochemical changes at the chiral centres in isoquinoline and indole alkaloids and related compounds are reviewed.

■ beta-Lactams as Synthons. Synthesis of Heterocycles via beta-Lactam Cleavage

Maghar Singh Manhas, Shantilal Gordhandas Amin, and Ajay Kumar Bose*

*Department of Chemistry and Chemical Engineering, Stevens Institute of Technology, Castle Point on the Hudson, Hoboken, NJ 07030, U.S.A.

Abstract

beta-Lactams show high chemical reactivity and ease of molecular rearrangement and are therefore potential synthons of value. The present communication reviews the relevant literature and describes observation made in our laboratory and elsewhere. Suitably substituted beta-Lactams can lead to multi-heteroatom cyclic compounds of various sizes including derivatives of carbostyril, coumarin, diazepin, oxazepin and thiazepin of potential interest to synthetic and medicinal chemists.

■ The Use of Isolated Enzymes in Heterocyclic Chemsitry

Kenneth L. Stuart*

*Department of Chemistry, Mona Campus, University of the West Indies, Mona, Kingston 7, Jamaica

Abstract

Current trends in the utilization of isolated enzymes in the synthesis and degradation of heterocyclic compounds are reviewed.

■ New Syntheses of Prostaglandis

Pierre Crabbé,* Eliezer Barreiro, Alicia Cruz, Jean-Pierre Deprès, Maria del Carmen Maena, and Andrew E. Greene

*Laboratorie de Chimie Organique, C. E. R. M. O., Université Scientifique et Médicale, B. P. n 53, 38041 Grenoble, France

Abstract

A detailed account of the total synthesis of prostaglandins by the tropolone approach is given. The preparation of novel modified prostaglandins, including 11-substituted and 11-nor-prostaglandins, is also mentioned.

■ Mass Spectroscopic Fragmentation Reactions, XIII: The Behavior of Sterically highly Hindered Porphyrins. — Mass Spectra of Sterically Hindered Porphyrins —

Reinhold Pesch and Herbert Budzikiewicz*

*Institut für Organische Chemie, Universität zu Köln, Greinstraße 4, D-50939 Köln 41, Germany

Abstract

It is shown that otherwise characteristic benzylic cleavage is reduced in importance as compared with complex fragmentation processes for compounds sterically hindered by 6,γ,7- substitution. Amongst these reactions are tetrahedralisation of C-β and (in case of chlorins) formation of a 7,8-double bond, both accompanied by multiple H migrations. A rationale is given for the occasionally contradicting influence of complexed metal ions reported in literature.

■ The Diterpenoid Alkaloids of Delphinium staphisagria

S. William Pelletier* and Naresh V. Mody

*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.

Abstract

The structure determination and chemistry of four C₁₉-diterpenoid alkaloids, delphinine (1), delphisine (9), delphidine (24) and delphirine (12), irolated from the seeds of Delphinium staphisagria by a combination of gradient pH extractions and chromotogrophic techniques, is summarized. The unusual ultraviolet absorption of pyrodelphonine (5) is discussed from the point of view of a photoreduction reaction and the ¹³C and ¹H nmr spectra. On the basis of the hydrolysis product of delphisine (9), the structures of neoline, chasmanine and homochasmanine have been revised to 11, 13 and 15, respectively. The structural elucidation of a new class of eight bis-diterpenoid alkaloids isolated from the mother liquors of D. staphisagria is discussed. The structure of staphisine as 27 has been established by a single-crystal X-ray analysis of the monomethiodide. Application of ¹³C and ¹H nmr spectroscopy to the remaining seven alkaloids led to the assignment of structures for staphidine (28), staphinine (29), staphimine (30), staphigine (31), staphirine (32), staphisagnine (33) and staphisagrine (34). These bis-diterpenoid alkaloids occur as methoxyl and demethoxyl pairs in D. staphisagria.

■ Diterpenoids of Isodon and Teucrium Plants

Eiichi Fujita,* Yoshimitsu Nagao, and Manabu Node

*Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

Abstract

The Chemistry on diterpenoids of the plants belonging to the genera Isodon and Teucrium (Labiatae) has recently been developed. This review deals mainly with our research works concerning isolation and characterization of new diterpenoids, their reaction and interconversion, synthesis, biosynthesis, and biological activity.

■ Examples of the Use of Fluorescent. Heterocycles in Chemistry and Biology

Richard W. Thomas and Nelson J. Leonard*

*Roger Adams Laboratory, School of Chemical Sciences, University of Illinois, 1209 West California Street, Urbana, IL 61801-3731, U.S.A.

Abstract

The application of fluorescent heterocycles to the study of chemical and biological systems is discussed. The spectroscopic properties of coumarins, pyrrolinones derived from fluorescamine, and nucleic acid base analogs, together with examples of their use, are described in detail.

■ Organoborane Heterocycles via Cyclic Hydroboration of Dienes

Ei-ichi Negishi, Surendra U. Kulkarni, and Herbert C. Brown*

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Hydroboration of dienes can give rise to heterocyclic organoboron derivatives or polymers depending upon the hydroborating agent and conditions used. It is advantageous to use bifunctional hydroborating agents such as thexylborane (BH₂) or monochloroborane etherate (BH₂Cl·OEt₂) for such cyclic hydroboration.

■ Reduction of Heterocyclic Compounds by Metal-Ammonia Solutions and Related Reagents

Arthur J. Birch* and Jacob Slobbe

*Research School of Chemistry, Institute of Advanced Studies, The Australian National University, GPO Box 414, Canberra, ACT 0200, Australia

Abstract

The theoretical and practical bases of the metal-ammonia and related reductions of heterocyclic compounds are reviewed. No attempt to summarise all extant results has been made, but rather a critical evaluation of possible procedures is illustrated by pertinent examples. The headings in order are:
Introduction, structure and reducibility
The addition of the first electron
Further reactions: (i) Protonation of A* (ii) Dianion formation (iii) Dimerisation
Cleavage reactions
Oxygen heterocycles
Sulphur heterocycles
Results of different proton availabilities
Uniquely available compounds