HETEROCYCLES

■ Synthesis of B-Nor-6-aza-12-thia-3-methoxy-estea-1,3,5(10),8-tetraene-12-dioxide-17-ol

Pramod S. Jogdeo and Gangadhar V. Bhide*

*Chemical Ecology Section, Bio-organic Division, Bhabha Atomic Research Centre, Trombay, Bombay 400 085, India

Abstract

A novel thia-azasteroid, B-nor-6-aza-12-thia-3-methoxy-estra-1,3,6(10),8-totraene-12-dioxide-17-ol (I) bas been synthesieed.

■ An Adventitious Synthesis of Pederinolactone

Jerrold Meinwald,* Michael Adams, and Angelina J. Duggan

*Department of Chemistry & Chemical Biology, Cornell University, Ithaca, NY 14853-1301, U.S.A.

Abstract

The synthesis of pederinolactone (2) is reported.

■ Nucleophilic Amination and Recyclization of the Indolizine Nucleus

Alexej N. Kost, Reva S. Sagitullin, and Sergej P. Gromov*

*Department of Chemistry, Moscow State University, Moscow 117234, Russia

Abstract

Treatment of 6- or 8-nitroindolizines with aqueous alcoholic alkaline solution forms 5- or 7-nitroindoles (III) by ring transformation. Primary or secondary amines reacted with 8-nitroindolizines (IV) to form δ-complexes which transformed into 5-amino-8-nitroindolizines (V) by air oxidation.

■ A New Synthesis of β-Lactams. Rearrangements of α-Diazo Thioesters

Vlasios Georgian,* Stephen K. Boyer, and Brooks Edwards

*Department of Chemistry, Tufts University, Medford, Massachusetts 02155, U.S.A.

Abstract

A new synthesis of alkylthio-substituted β-lactams by the rearrangement of α-diazo thioesters has been developed.

■ Reaction of N-Diazoacetyl-Δ³-piperideines: Formation of 1-Azabicyclo[4.2.0]-3-(and 4)-octen-8-ones (1-Carba-Δ¹[and Δ²]-cephems)

Vlasios Georgian* and William H. Koster

*Department of Chemistry, Tufts University, Medford, Massachusetts 02155, U.S.A.

Abstract

The formation of 1-azabicyclo[4.2.0]-3-(and 4)-octen-8-ones from N-diazoacetyl-δ³ piperideine is discussed.

■ Bridged Quinuclidines: Synthesis of 5-Azatricyclo[3.2.1.0^2,7]octane. Incorporation of a Bridged Quinuclidine into the Cinchona Alkaloid Skeleton

Vlasios Georgian* and William H. Koster

*Department of Chemistry, Tufts University, Medford, Massachusetts 02155, U.S.A.

Abstract

Incorporation of a bridged quinuclidine into the cinchona alkaloid skeleton is discussed.

■ Synthesis of 4-Aza-6-thiabicyclo[3.3.0]octane

Gerhard G. Habermehl* and Wolfgang Ecsy

*Institut für Organische Chemie, Technische Hochschule Darmstadt, Petersenstrasse. 22 64287 Darmstadt, Germany

Abstract

Starting from cysteine, 4-aza-2-oxa-6-thiabicyclo[3.3.0]octane has been synthesized in a four step synthesis; the over all yield is 40 %.

■ Recent Advances in Quinuclidine Chemistry

Lenoid Yakhontov*

*S. Ordzhonikidze All-Union Chemcal-Pharmaceutical Research Intitute, Moscow, Russia

Abstract

This article aims to review the published and own results in quinuclidine chemistry over recent ten years. The main attention of the paper is concentrated on some peculiarities in reactivity of quinuclidine derivatives and on relationships between the chemical structure and biological activity.

■ Chemistry of C₄-Functionalized 1,3,2-Oxazaphosphorinane 2-Oxides Related to the Active Metabolite of Cyclophosphamide

Akira Takamizawa,* Saichi Matsumoto, Tsuyoshi Iwata, and Itsuo Makino

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

Abstract

Current status of synthetic and stereochemical studies of the activated species of cyclophos- phamide and related 1,3,2-oxazaphosphorinane antitumor alkylating agents is reviewed.

■ Chemistry of N-Nitrosiomines

Kin-ya Akiba* and Naoki Inamoto

*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan

Abstract

N-Nitrosoimines of general formula, R¹R²C=N-N=O, are thermally unstable and apt to decompose to the corresponding carbonyl compounds and nitrogen. When the nitrosoimines are contained in heterocycles such as thiazoline, thiadiazoline, pyrrolidine, and etc., they are stable for isolation and show mesoionic character. This article gives
1. Preparation and Spectral Character
2. Thermal and Photochemical Decomposition
3. Reduction with Lithium Aluminum Hydride
4. Reactions with Grignard Reagents and Organolithiums
5. Miscellaneous Reactions

■ New Orally Active Cephalosporins

Riccardo Scartazzini* and Hans Bickel

*Pharmaceuticals Division, Research Department, Ciba-Geigy Limited, CH-4002 Basel, Switzerland

Abstract

The synthesis of cephalosporins modified at C-3 and the effect of the substituents on the oral absorption is reviewed. Of the structural variants studied in the author’s laboratory the 3-methoxy derivatives are of particular interest.

■ Aromatic Amine N-Oxides in Syntheses of Nucleosides and Nucleotides

Yoshihisa Mizuno,* Kazuyoshi Ikeda, Takeshi Endo, and Kiyomi Tsuchida

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

A new protecting group, the 2-picolyl 1-oxide (PO) group, is quite stable both in alkaline and in acidic media but readily removable by treatment by acid anhydride. This PO group is useful in cases where the benzyl group does not work well. By the use of this protecting group, a variety of nucleo-base analogs, nucleosides, and nucleotides have been prepared. The potentiality of this group as “functionalized” protecting group which might assist acylation (including phosphorylation) of hydroxyl groups which are located in its neighborhood is also discussed.
1. Scope of PO Protection
2. Introduction of PO Group into Substrates
3. Deblocking and Controlled Acylation
4. Neighboring Group Participation of N-Oxide in Acylation

■ Synthesis of Oligoribonucleotides via Phosphotriester Intermediates

J. H. van Boom*

*Gorlaeus Laboratories, Rijks Universiteit, Postbus 75, Leiden, The Netherlands

Abstract

The synthesis of naturally occurring oligoribonucleotides still presents, despite many efforts made in the past, a tremendous challenge to organic chemists. The reason for the slow progress in the synthesis of RNA, in comparison with DNA, can be ascribed to the complexity and diversity of these compounds. DNA’s lack the 2’-OH function and are, in most cases, polymers derived from four comnon d-nucleosides. These structural elements highly facilitate, from a chemical point of view, the preparation of properly-protected d-nucleosides and the formation of 3’- 5’ internucleotide phosphodiester bonds. On the contrary, the presence of an additional 2’-OH group in ribonucleosides and the fact that RNA’s, from natural origin, not only contain the four comnon but also modified nucleosides make the synthesis of RNA very complex and elahorate.
The aim of this review¹ is to show that most of the different types of naturally occurring RNA can be synthesized exclusively via phosphotriester intermediates.
Therefore, in order to make the synthesis of RNA via phosphotriester intermediates more accessible, it would be of prime importance to have at our disposal:
1. general and non timeconsuming procedures for the nrenaration of suitably-protected ribonucleosides(tides);
2. efficient phosphorylating and activating agents which are necessary for the introduction of phosphotriester functions;
3. selective deblocking procedures;
4. rapid and reliable analytical methods to assess homogeneity and structural proof of completely deblocked oligoribonucleotides.

■ Non-bonded Attraction and the Conformation of Aromatic Amino Acid Derivatives

Ajay Kumar Bose,* Maghar Singh Manhas, Robert Franklyn Tavares, James Morris van der Veen, and Hideji Fujiwara

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

Abstract

NMR and X-ray crystallographic studies have shown that hydantoins derived from aromatic amino acids prefer folded conformation in solution because of non-bonded attraction between the Π electrons and dipoles in the hydantoin ring. The favored conformation in the crystalline state may be different from that in solution. In a crystal, the effect of intramolecular non-bonded attraction may be counter-balanced by other factors, such as, lattice forces, hydrogen bonding and intermolecular interaction. Folded conformation is also found in cyclic dipeptides containing one or more aromatic amino acid residues. It is necessary to take into consideration non-bonded attraction as well as steric repulsion in studying the conformation of peptides and enzyme-substrate binding.

■ Stereoelectronic Control in Hydrolytic Reactions

Pierre Deslongchamps*

*Department of Chemistry, University of Sherbrooke, Sherbrooke, Quebec, J5K 2R1, Canada

Abstract

Experiments are described which show that the stereochemistry and the ionic state of tetrahedral intermediates, the orientation of non-bonded electron pairs, and the relative energy barriers for cleavage and for molecular rotation are the key parameters in the stereoelectronically controlled cleavage of tetrahedral intermediates formed in the hydrolysis of esters and amides.

■ Heteropentalenes and Heterocyclic Ferrocenes

Heinrich Volz* and Heinrich Kowarsch

*Institute für Organic Chemie, Universität Karlsruhe Lehrstubl I, Richard-Willstätter-Allee, 76131 Karlsruhe, Germany

Abstract

The synthesis and properties of heteropentalene anions with one heteroatom and heterocyclic ferrocenes with a fused Π-heterocycle have been reviewed.

■ Syntheses and Rearrangements of Some Four-Membered Heterocyclic Compounds

B. D. Tilak* and V. N. Gogte

*National Chemical Laboratory, Pashan Road, Pune 411 008, India