摘要:

Hot off the press Robert A. Hill and Marie Claire Parker Department of Chemistry Glasgow University Glasgow UK G12 8QQ. E-mail bobh@chem.gla.ac.uk m.parker@chem.gla.ac.uk The first examples of sesquiterpenoid-flavonoids such as fissistigmatin A 1 have been isolated from Fissistigma bracteolatum a Vietnamese folk-medicinal plant (G. Adam and co-workers Tetrahedron 2000 56 865). The cassane quinomethane derivative 2 isolated from the root bark of Bobgunnia madagascariensis shows strong antifungal properties towards human pathogenic fungi such as the yeast Candida albicans (K. Hostettmann and co-workers Helv. Chim. Acta 2000 83 407). The novel alkaloid prioline 3 from the roots of Salvia prionitis is likely to be derived from a degraded abietane derivative (J.-S.Zhang and co-workers J. Nat. Prod. 2000 63 139). A group of metabolites from the sponge Hamigera taragaensis such as hamigeran A 4 are also of diterpenoid origin (R. C. Cambie and co-workers J. Nat. Prod. 2000 63 79). The biosynthetic origin of sarcopetalolide 5 from Croton sarcopetalus is probably through a pimarane derivative (P. Joseph-Nathan and co-workers J. Nat. Prod. 2000 63 222). Columbiasin A 6 from Pseudopterogorgia elisabethae possesses a novel tetracyclic diterpenoid skeleton (A. D. Rodríguez and C. Ramírez Org. Lett. 2000 2 507). The tetranortriterpenoid delevoyin C 7 from Entandrophragma delevoyi contains a cyclobutane ring incorporating C-19 (D. A. Mulholland et al. Phytochemistry 2000 53 465). Pterocarposide 8 from Pterocarpus marsupium is the first example of an isoaurone C-glucoside (S.S. Handa et al. Tetrahedron Lett. 2000 41 1579). The flavonoid tephrorin A 9 a constituent of Tephrosia purpurea contains an unusual tetrahydrofuranyl moiety (A. D. Kinghorn and co-workers Org. Lett. 2000 2 515). The culture broth of the insect pathogenic fungus Cordyceps pseudomilitaris contains cordyanhydride B 10 which is the first example of a nonadride containing three C9-units (M. Isaka et al. Tetrahedron Lett. 2000 41 1657). The interesting acetylenic compound sterehirsutinal 11 is a metabolite of the phytopathogenic fungus Stereum hirsutum that is involved in the grapevine disease called esca (R. Tabacchi and co-workers Phytochemistry 2000 53 571). A new dimeric coumarin 12 has been isolated from the peel of Citrus lumia (M.Ju-ichi and co-workers Heterocycles 2000 53 441). The structure of the dimeric coumarin 12 was confirmed by X-ray crystal structure analysis and it has been synthesised by UV irradiation of the co-occurring bergapten 13. Buergerinin G 14 from Scrophularia buergeriana has a novel carbon skeleton (D.-Y. Zhu and co-workers Tetrahedron Lett. 2000 41 1069). The structure of buergerinin G 14 was established by X-ray crystallographic analysis. Alutacenoic acids A 15 and B 16 are cyclopropenones obtained from the fungus Eupenicillium alutaceum (H. Kogen et al. J. Am. Chem. Soc. 2000 122 1842). Alutacenoic acids A 15 and B 16 are potent factor XIIIa inhibitors. The novel tetramic acid melophlin B 17 isolated from the marine sponge Melophlus sarassinorum has been shown to reverse the iii Nat.Prod. Rep. 2000 17 DOI 10.1039/b002517h This journal is © The Royal Society of Chemistry 2000 phenotype of ras-transformed cells (M. Kobayashi and coworkers Tetrahedron 2000 56 1833). Peloruside A 18 is a macrolide from a Mycale species that shows cytotoxic activity in the nanomolar range (P. T. Northcote and co-workers J. Org. Chem. 2000 65 445). The dumbbell-shaped dimeric cyclohexapeptide chloptosin 19 isolated from a Streptomyces species was found to induce apoptosis in apoptosis-resistant cell line AsPC-1 (K. Umezawa et al. J. Org. Chem. 2000 65 459). The mechanisms of action of the bleomycin group of antitumour antibiotics has been reviewed (S.M. Hecht J. Nat. Prod. 2000 63 158). A precursor of the dysidenin metabolites herbacic acid 20 has been found in Dysidea herbacea (J. B. MacMillan and T. F. Molinski J. Nat. Prod. 2000 63 155). Labelling studies on brubromycin 21 from Streptomyces species A1 do not distinguish between a biosynthesis involving two polyketide chains or the oxidative cleavage of a single polyketide chain (A. Nat. Prod. Rep. 2000 17 iv Zeeck and co-workers Eur. J. Org. Chem. 2000 729). Mutation experiments are continuing to give greater understanding of terpenoid biosynthesis. Studies on lanosterol synthase (S. P. T. Matsuda and co-workers Org. Lett. 2000 2 339) and hopane synthase (T. Hoshino et al. Chem. Commun. 2000 441) indicate that active site residues control cyclisation through steric effects.The synthesis and characterisation of a new photolabile precursor of glycine 22 is reported by C. Grewer et al. (Biochemistry 2000 39 2063) as a tool for the chemical kinetic investigations of the glycine receptor. The a-carboxy group of glycine is covalently coupled to the a-carboxy-2-nitrobenzyl (aCNB) protecting group. Photolysis of the glycine derivative 22 with UV light produces free glycine. The glycine derivative 22 is the first in a series of photoprotected glycines that has the required properties for use with chemical kinetic methods to investigate glycine-activated cell surface receptors. The ester 22 can be photolysed rapidly and efficiently and preliminary results suggest that it will be a useful tool for determining rate constants of channel opening and closing.A novel method for increasing the catalytic performance of enzymes used for organic synthesis in organic media has been reported (J. Partridge et al. J. Chem. Soc. Perkin Trans. 2 2000 465). The method describes the use of solid-state proton/ sodium buffers termed “chemical pH stats”. The solid-state buffers were able to control the protonation-state of enzymes such as subtilisin Carlsberg and a-chymotrypsin in polar organic media (THF and MeCN). The buffers prevent detrimental changes to enzyme activity caused by the presence or build up of acids or bases in the organic reaction that can often go undetected. Both the (R) and (S) enantiomers of 2-ethylhexan-1-ol 23 and 2-ethylhex-5-en-1-ol 24 can be prepared in good yields and high enantiomeric excess via the lipase-catalysed transacetylation of the racemic primary alcohols using vinyl acetate (Scheme 1) (K.Baczko and C. Larpent J. Chem. Soc. Perkin Trans. 2 2000, Scheme 1 521). The enantioselectivity is greatly enhanced by the presence of a terminal double bond in 2-ethylhex-5-en-1-ol 24 and surprisingly a decrease of 30 ºC from 0 °C enhances the enantioselectivity without any appreciable loss in catalytic activity. P. D. Bailey and co-workers have described a template that is a general model for the orientation of the key binding features of the peptide transporter protein PepT1 which is thought to be a trans-membrane protein (Angew. Chem. Int.Ed. 2000 39 506). The model identifies four key binding sites whilst the 3-D layout of the template is defined by other stereochemical and conformational features. This model appears to account for all of the substrate specificities relating to PepT1. Using this template the authors suggest that it may be possible to predict whether substrates will have high medium or low affinity for PepT1. The key requisites in chemoinformatics specifically for the prediction of physicochemical properties of “drug-like” molecules have been outlined by J. F. Blake (Curr. Opin. Biotechnol. 2000 11 104). The review covers computational approaches to the prediction of various physicochemical properties of complex organic molecules from their molecular structures without the need of any experimentally derived parameters.The computational approaches described are aimed at the prediction of the physicochemical properties that play a critical role in determining the oral absorption characteristics of therapeutic agents namely aqueous thermodynamic solubility and permeability across biological membranes. The proteolytic enzyme pepsin can be encapsulated via electrostatic interaction in thermally evaporated fatty lipid matrices of octadecylamine by simple immersion of the lipid film in the protein solution under mild preparative conditions (Gole et al. Chem. Commun. 2000 297). The encapsulated enzyme showed good biocatalytic activity using hemoglobin as the substrate. The enzyme molecules could be encapsulated into the octadecylamine film without significant distortion of the native structure.The design of rigid amphiphiles for membrane protein manipulation has been reported (M. P. Krebs and co-workers Angew. Chem. Int. Ed. 2000 39 758). A “tripod amphiphile” based on a rigid quaternary carbon centre 25 was synthesised and evidence was presented that these amphiphiles can solubilise two non-homologous membrane proteins (bacteriorhodopsin and bovine rhodopsin) with the protein folding remaining intact. The paper highlights the need for the design of amphiphiles as an alternative to commercially available detergents. Tripod amphiphiles are built around a quaternary carbon atom that bears one polar and three nonpolar appendages. The quaternary carbon atom therefore introduces a substantial conformational restriction relative to the linear alkyl chains common among detergents commonly used for protein solubilisation.The immobilisation of proteins within the galleries of layered a-zirconium phosphate has been described (C. V. Kumar and A. Chaudhari J. Am. Chem. Soc. 2000 122 830). The immobilisation of a number of proteins including haemoglobin glucose oxidase and lysozyme at the interlayer regions of a-ZrP could be achieved under ambient conditions from buffer solution. The proteins retained their structure and activity after immobilisation. They also noted that the interlayer spacing observed for the protein a-ZrP composites showed a strong correlation with the average size of the protein. N. C. Price (Curr. Opin. Biotechnol. 2000 11 29) has reviewed the conformational issues that relate to protein characterisation. The principal techniques for determining protein conformation flexibility and the current theories of the mechanisms by which proteins fold are discussed together with strategies that can be adopted for the preservation of conformational integrity. Issues relating to the analysis of protein conformation for biotherapeutics are also addressed. v Nat. Prod. Rep. 2000 17

ISSN:0265-0568    

DOI:10.1039/A003HOPY

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Book reviews Biocatalysts for Fine Chemical Synthesis Ed. S. M. Roberts Wiley 1999 800 pp. price £250 ISBN 0-471-97901-5 The aim of Biocatalysts for Fine Chemical Syntheses is to provide a compendium of “recipes” for biotransformations in a similar vein to Organic Syntheses routinely used by synthetic chemists. From 1992–1997 Preparative Biotransformations was published in loose-leaf format with detailed protocols on the use of biotransformations in organic synthesis. This new book includes a collection of procedures originally published in the loose-leaf manual as well as an interesting and informative review highlighting key advances in the field reported in the literature of 1996. I find this new book a much improved format. Biotransformations represent a powerful synthetic tool to complement other methodology in modern synthetic organic chemistry.The use of lipases and esterases in kinetic resolutions is well established and there have been many exciting advances in the use of enzymes to catalyse further important transformations including reductions Baeyer–Villiger oxidations carbon– carbon bond forming reactions hydrolyses of amides and nitriles and dynamic kinetic resolutions using whole cell systems and isolated enzymes. In addition enzymes are becoming increasingly important in carbohydrate synthesis and modification. Many of these catalysts are now commercially available making them readily accessible to the synthetic chemist. The reactions are often as simple (if not easier!) to perform than more widely accepted processes and give good yields of products with excellent ees.Despite all these advances many chemists view biotransformations with a certain scepticism or would only contemplate the use of enzymes as a last resort. To use biotransformations routinely alongside our more classical repertoire of reagents and reactions will greatly enhance our creativity and efficiency in asymmetric synthesis and as stated in the foreward of this book “Crucial to the undersue of biotransformations is convincing scientists at the most important stage of their training that they can make use of biotransformations as a routine part of synthetic and development projects.” There is no doubt that everyone who delves into Biocatalysts for Fine Chemicals Synthesis will gain not only an appreciation of the varied applications of enzymes to prepare chiral molecules in enantioenriched form but also valuable practical tips in utilising these catalysts.Biocatalysts for Fine Chemicals Synthesis begins with a graphical abstract clearly illustrating the transformations detailed within the book and is followed by a well-written review of the literature published in 1996. The main body of the book is then divided into five chapters. Chapter one is dedicated to enzyme catalysed hydrolysis and esterification reactions and not surprisingly is the longest. The chapter is further subdivided into sections relating to specific topics e.g. preparation and hydrolysis of esters nitrile hydrolysis and amide hydrolysis.Examples of individual reactions within each class are discussed in detail. Each reaction is clearly presented with relevant background information and references followed by detailed experimental protocols which may be readily followed by chemists with little practical experience. Of particular importance to the non-specialist in the field is the commercial source of the enzyme and which of the bewildering array of for example lipases specified in a catalogue should be purchased. This information is given for each experiment. The following three chapters are presented in the same clear and informative style as chapter one and describe enzyme catalysed reductions (using bakers’ yeast and isolated enzymes) oxidations (including for example epoxidations hydroxylation and hydroperoxidation of double bonds and sulfur oxidation) and carbon–carbon bond forming reactions (such as aldolase catalysed processes and the preparation of cyanohydrins).Finally chapter five outlines two case studies (a comparison of biocatalytic routes to (S)-hept-6-yn-2-ol a synthon to brefeldin A and a comparison between the use of two lipases in the enantioselective transesterification of glycidic esters) and a section on the properties and determination of protein content of commercially available lipase preparations. This book will prove extremely valuable for research scientists with little experience in the use of enzymes in organic synthesis as well as for specialists in the field. The clarity of the descriptions of the experiments should enable the transformations to be reproduced readily and the less expensive experiments could be usefully incorporated into an undergraduate laboratory training programme so giving students a flavour of the immense potential of enzymes in synthesis.I strongly recommend Biocatalysts for Fine Chemicals Synthesis for libraries both within industry and universities. Chris Willis University of Bristol UK Chemistry of Natural Products A Unified Approach N. R. Krishnaswamy Universities Press (India) Ltd Hyderabad 1999 pp. xii + 224 £10.95 ISBN 81-7371-093-7 For many years there have been attempts to teach the diverse chemistry of the various groups of natural product such as alkaloids terpenoids polyketides and oxygen heterocycles in a unified manner.It is the object of this book to do this under the headings of structure stereochemistry reactions and rearrangements synthesis biosynthesis and biological significance. The first chapter describes some of the evidence for the structure of ten natural products drawn from amongst the alkaloids terpenoids and oxygen heterocycles. These are each treated separately with the complexities of strychnine coming first. It is a pity that the author has chosen to present structure elucidation as a series of case histories because there are some unifying aspects of structure elucidation which are lost. For example in determining the underlying carbon skeleton of a natural product there are general strategies of structural simplification that have widespread application.It is also important to see the structure elucidation of a natural product in the context of the work which was going on at the same time. There are many examples of a series of structures falling into place within a short time of each other as a result of the development of a particular strategy such as dehydrogenation. The following chapters on stereochemistry reactions and synthesis use a similar case history approach. Here again there are potential unifying features such as the advent of nuclear magnetic resonance spectroscopy which could have been used to bring topics together. The two references to the use of the 315 Nat. Prod. Rep. 2000 17 129 the data given are not always sufficient for a unique answer.In problem 7.6 the answer states that the position of the angular methyl group follows from an application of the isoprene rule. Unfortunately the structure does not follow the simple isoprene rule. The book contains a number of mistakes particularly in the diagrams (e.g. Cr2O3 for chromium trioxide structure 4.5.4). Consequently I regret that I am unable to give this book more than a qualified recommendation. Karplus equation (pages 62 and 76) are two examples in which the interpretation is ambiguous whilst the nuclear Overhauser effect receives only one mention without any indication of an application. The chapter on biosynthesis is restricted to a description of the benzylisoquinoline alkaloids and the shikimic acid and mevalonoid pathways. There is no description of polyketide biosynthesis or of the recently discovered nonmevalonoid pathway to terpenoids. Each section is followed by suggestions for further reading although the references to the literature are almost all prior to 1990. The book concludes with a series of problems. However James R. Hanson University of Sussex UK Nat. Prod. Rep. 2000 17 129 316

ISSN:0265-0568    

DOI:10.1039/a003bkry

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

David Newman was born in Grays, Essex, UK. His initial training was as ananalyst (GRIC) followed by an MSc in Organic Chemistry (University ofLiverpool) and then after some time in the UK chemical industry, a DPhil inMicrobial Chemistry from the University of Sussex in 1968. Following twoyears of postdoctoral studies on the structure of electron transportproteins at the University of Georgia, USA, he worked with Smith Kline andFrench in Philadelphia, PA, as a biological chemist predominantly in thearea of antibiotic discovery. During this time period, he obtained an MLSin Information Sciences in 1977 from Drexel University, Philadelphia, PA.Following the discontinuance of antibiotic discovery programs at SKF, heworked for a number of US-based pharmaceutical companies innatural-products based discovery programs in anti-infectives and cancertreatments, and joined the Natural Products Branch of the NCI in 1991. Heis responsible for the marine and microbial collection programs of the NCIand in concert with Gordon Cragg, for the NCI’s Open and ActiveRepository programs. His scientific interests are in the discovery andhistory of novel natural products as drug leads in the anti-infective andcancer areas, in novel delivery methods for such agents and in theapplication of information technologies to drug discovery. In conjunctionwith Gordon Cragg, he has established collaborations between the NationalCancer Institute and organizations in many countries promoting drugdiscovery from their natural resources. He has published over 50 papers andpatents that are related to these interests and is both an UK CharteredChemist and an UK Chartered Biologist.

ISSN:0265-0568    

出版商:RSC    

年代:1999

数据来源: RSC