Georg Thieme Verlag Research Articles

Das turbulente Leben von Giorgos (Georg) Higoumenakis (1895 – 1983), Entdecker des Higoumenakis-Zeichens in später kongenitaler Syphilis und Pionier in der Forschung zur Leishmaniose

Das Higoumenakis-Zeichen in später kongenitaler Syphilis beschreibt die Vergrößerung des sternalen Endes der Klavikula aufgrund einer chronischen Periostitis. Es wurde von dem griechischen Dermatologen Giorgios Higoumenakis (1895 – 1983) in den späten 20er-Jahren des letzten Jahrhunderts beschrieben und seitdem von vielen Dermatologen erwähnt. Higoumenakis war außerdem ein bedeutender Spezialist auf den Feldern der Leishmaniose und der Psoriasis. In dieser Veröffentlichung beschreiben wir das Zeichen, berichten aber vor allem über Leben und Wirken von Giorgios Higoumenakis, welche in der wissenschaftlichen Literatur sehr kurz kommen. Sein Leben war abenteuerreich und turbulent. Er forschte in Griechenland, Deutschland und Frankreich unter berühmten Lehrern, produzierte viele wissenschaftliche Publikationen, hielt schweren persönlichen Konflikten mit dem griechischen akademischen System stand und wurde letzlich griechischer Gesundheitsminister. Diese Persönlichkeit verdient eine Beschreibung und Würdigung ihrer Leistungen, denn sie ist ein fester Bestandteil der modernen griechischen Medizin.

Regioselective Synthesis of Bromo-Substituted 3-Arylcoumarins

Regioselective syntheses of 3-arylcoumarins possessing a bromine substituent either on the 3-aryl ring, the coumarin moiety or on a lateral chain of a coumarin is reported. The regioselectivity is influenced by the substituents present in the substrates. Two different bromination methods are described and compared. Perkin condensation of 5-methylsalicylaldehyde and phenylacetic acid or para-methoxyphenylacetic acid affords the desired coumarins. Three different bromine substitution patterns are accessed starting from 5-methylsalicylaldehyde. © Georg Thieme Verlag Stuttgart.

The First Closure of the Persistent Ductus Arteriosus

Congenital heart disease began to be a treatable condition when, in 1938, Robert Edward Gross first successfully ligated a persistent ductus arteriosus. This overview traces the historical development from Munro's first idea of how to close a patent ductus, presented in 1907, to the clinical ligation or division of the ductus. Surgical treatment of the infected ductus began with an unsuccessful attempt by Strieder, but it was not until Tubbs' and Touroff's successful operations that it was actually accomplished.

4-Iminocyclobutenones: Synthesis and Building-Blocks of Aminohydroquinones and Annulated Quinolines

Two methods are presented for the synthesis of the title compounds starting from cyclobutenediones: an alkoxide substitution approach and a Staudinger reaction. Unsaturated lithiumorganyls may be added to the remaining carbonyl group and on heating lead to ring enlargement in a cascading process. 4-Alkenyl or 4-aryl derivatives yield aminophenols or -naphthols; 4-alkynyl compounds give cyclopenta-annulated quinolines. © Georg Thieme Verlag Stuttgart.

ESGE Newsletter

ESGE will again share a booth with the Publishers of Endoscopy, Georg Thieme Verlag, at the DDW. If you are in New Orleans, please do drop by the booth (529).

Cyanogen Bromide as Dehydrosulfurizing Agent for the Synthesis of Nβ-Fmoc-Amino Alkyl Isonitriles from Nβ-Fmoc-Amino Alkyl Thioformamides

Synthetically useful NI²-Fmoc amino alkyl isonitriles are prepared conveniently from NI²-Fmoc amino alkyl thioformamides via a cyanogen bromide mediated dehydrosulfurization. The reaction is fast, clean, and yields are good. © Georg Thieme Verlag Stuttgart - New York.

Terminologia anatomica: international anatomical terminology and Terminologia Histologica: International Terms for Human Cytology and Histology

Terminologia anatomica: international anatomical terminology By the Federative Committee on Anatomical Terminology (FCAT) . Stuttgart : Georg Thieme Verlag . ISBN-10: 3-13-114361-4 . ISBN-13: 978-3-13-114361-7 . 300 pp . 1998 . £48.62 hardback . Terminologia Histologica: International Terms for Human Cytology and Histology By the Federative International Committee on Anatomical Terminology (FICAT) . Philadelphia : Wolters Kluwer/Lippincott Williams & Wilkins . ISBN-10: 0-7817-6610-9 . ISBN-13: 978-0-7817-6610-4 . 213 pp . 2008 . £21.00 hardback . Terminologia Anatomica (TA) is the international standard on human anatomical terminology. It was developed by the Federative Committee on Anatomical Terminology (FCAT) and the International Federation of Associations of Anatomists (IFAA) and was released in 1998. It supersedes the previous standard, Nomina Anatomica. Terminologia Histologica (TH) is a companion text to TA developed by the renamed Federative International Committee on Anatomical Terminology (FICAT) and was published in 2008. TA contains terminology for about 7500 human gross (macroscopic) anatomical structures, while TH contains terminology for cellular structures, tissue and organs at the microscopic level. The books present the Latin term for each structure accompanied by the term in current usage in English-speaking countries. Where spelling varies between UK and USA English the term is marked with a small triangle, but only the UK spelling is listed. (The meaning of this triangle is not explained, though after a few examples it becomes clear.) TA begins with a section listing general terms, parts of the body and the terms used for planes, lines and regions. In the next section the terminology is divided into systems: Bones, Joints, Muscles, Alimentary system, Respiratory system, Thoracic cavity, Urinary system, Genital systems, Abdominopelvic cavity, Endocrine glands, Cardiovascular system, Lymphoid system, Nervous system, Sense organs and the Integument. The book also has a chapter giving an interesting brief history of the efforts to develop an internationally recognized standard for anatomical terminology. Following the terminology lists there are indexes of eponyms, Latin terms, and English terms. TH follows a similar logical structure starting with cytology terms, then general histology followed by each of the organ systems in similar order to that found in TA, and ending with the same three indexes. Anatomical and histological terminology is rooted in the classical languages, especially Latin. This can be increasingly challenging to doctors and scientists with the demise in the teaching of Latin at school, as this means that terms have to be learned, often with no background knowledge of the meaning of the Latin to make the learning easier, or of grammatical rules that make sense of plural terms and the agreement of adjectives with their nouns. This in turn leads to an increasing use of the English terms which brings an increased risk of confusion (especially when co-workers of different nationalities interact). Matters are further confused for the student/doctor/scientist by different reference sources using either common ‘anglicized’ versions of terminology or the formal Latin terms. These two books form a useful bridge between the two, and by presenting the standard terms for both Latin and English, they form a very useful reference for avoiding misunderstanding. It is certainly my opinion that this represents an essential source of reference for anyone studying the anatomical sciences. The indexes form an invaluable tool for finding either the Latin or English term. There is a CD-ROM version of TA that would make this even easier, and would therefore be the version I would recommend, while TH comes with the CD-ROM included in the price. In my opinion it would be very useful if the publisher or FICAT made the contents of both of these texts available as an online service, especially as TA seems to be no longer freely available. The only real criticism I have is that while the authors acknowledge that UK and USA spelling of English terminology is equally valid, and go to the trouble of marking entries where there is a difference between the two, they only list the UK version. It would have been much more satisfactory to list both, especially for readers in the USA.

Synthesis and Biological Evaluation of 6-Substituted Purinylcarbanucleosides with a Cyclopenta[b]thiophene Pseudosugar

The first members of a new family of heterocarbobicyclic nucleoside analogues have been synthesized from the cis/trans mixture of (4-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-6-yl)methanols (cis/trans-7). The separation of the cis and trans intermediates during the preparation of the 6-chloropurine derivatives allowed a separate preparation of the purine heterocarbanucleosides cis-10 and trans-11, from which cis-12-14 and trans-16-18 were obtained by replacement of the 6-chloro substituent with amino, hydroxy, and cyclopropylamino groups. Additionally, the 6-phenylpurinyl analogues cis-15 and trans-19 were prepared from cis-10 and trans-11 using Suzuki-Miyaura methodology. In tests of antiviral and cytostatic activities, compound 11 showed cytostatic activity against Molt4/C8 human T lymphoblastic leukemia cells. Antiviral activity was shown by compounds 15 and 19 against Punta Toro virus and Coxackie virus B4 (compound 11). © Georg Thieme Verlag Stuttgart.

The Art of the Soluble: Synthetic Problems from Industry as a Springboard for the Discovery of New Chemical Reactions

This account relates the thought processes that went into solving synthetic problems, mostly related to steroids, submitted by industry and, in many cases, the evolution of the solutions into new reactions more generally useful in organic synthesis. A strong emphasis is placed on mechanistic considerations and serendipitous findings as the main basis for constructing working hypotheses from which novel reactions were derived. 1 Introduction 2 Early Steroid Problems 2.1 A Pleasant Encounter with Isocyanides 2.2 The Nitro Route to Corticosteroids 2.3 Explorations in Nitro Chemistry 3 The 16s-Methyl Problem 4 A Problem of Bile Acid Side-Chain Degradation 4.1 Planned and Unexpected Oxazoline Chemistry 4.2 New Reactions of Sulfines 4.3 An Unusual Route to Trifluoromethyl Ketones 5 From Enamides to Radical Chemistry 6 Solutions Waiting for Problems. © Georg Thieme Verlag Stuttgart.

One-Pot Synthesis of Ureido Peptides and Urea-Tethered Glycosylated Amino Acids Employing Deoxo-Fluor and TMSN3

A facile one-pot procedure for the synthesis of urea-linked peptidomimetics and neoglycopeptides under Curtius rearrangement conditions employing Deoxo-Fluor and TMSN3 is described. The method is efficient and circumvents the isolation of acyl azide and isocyanate intermediates. The rearrangement of the in situ generated acyl azide via the acyl fluoride was carried out under ultrasonication followed by amine capture to insert a urea bond. The protocol worked well with all the common N-urethane-protected amino acids and also with a sugar-6-acid. © Georg Thieme Verlag Stuttgart.

A Radical Clock for Reactions of Epoxy Derivatives Induced by Titanocene Chloride

A new radical clock based on pinene derivatives has been designed to measure the radical cyclization rate onto cyano and carbonyl groups and the radical elimination rate of OR and CN. In this system, the known rate constant of cyclobutylcarbinyl radical cleavage is used as the internal clock. At room temperature, the cyclization rate constants for 4-exo and 5-exo processes onto nitrile and aldehyde carbonyl groups are in the order of 107 to 108 s-1. The radical elimination rate constants for CN, OH, OCHO, and OAc are in the order of 105 to 108 s -1. © Georg Thieme Verlag Stuttgart.

Generation and Intermolecular Additions of Pyridylmethyl Radicals

2-, 3-, or 4-Pyridylmethyl radicals can be made to add to nonactivated alkenes to give a variety of otherwise inaccessible pyridine derivatives. Bicyclic structures can be obtained by combining the radical addition with ionic ring-closure steps. © Georg Thieme Verlag Stuttgart.

Synthesis of Pyrenolide D Analogues

We present a short, enantiospecific synthesis of four hydroxylated analogues of pyrenolide D from D-glucose based on furan oxidative spirocyclisation. © Georg Thieme Verlag Stuttgart.

A One-Pot, Ugi Four-Component Synthesis of 2(3H)-Oxazolone 4-Carboxamides

Ugi reaction between arylglyoxals, anilines, cyclohexyl isocyanide and trichloroacetic acid in dichloromethane, in the presence of molecular sieves, afforded 2(3H)-oxazolone 4-carboxamides in good yields by a one-pot process that involved an in situ spontaneous cyclization of the Ugi product through an intermediate ketone enolate and the chloroacetate carbonyl group. The synthesis is based on the ability of the trichloroacetyl group to function as a masked carbonic acid surrogate. © Georg Thieme Verlag Stuttgart.

Stereoselective Radical Cascade Cyclizations of Unsaturated Epoxynitriles: Quadruple Radical Cyclization Terminated by a 4-exo Process onto Nitrile

Radical cascade cyclizations of unsaturated epoxynitriles induced by titanocene chloride proceed in good yields and with excellent diastereoselectivities. From three to seven stereocenters were created by the reaction and a single isomeric product was obtained from most of the substrates examined. The relative configuration of the products is consistent with cyclization occurring via a chair-like transition state. The termination of the radical cascade reaction by 4-exo, 5-exo or 6-exo cyclization onto nitrile is remarkable. © Georg Thieme Verlag Stuttgart.

An Efficient Synthetic Route to N-Glycosylamino Acids Using Nα-Fmoc-Asp/Glu-5-oxazolidinone as Internal Protection

A new facile synthetic route to prepare N-glycosylamino acids in fewer steps is reported. 5-Oxazolidinone served as an effective protecting moiety for NI±-Fmoc-Asp/Glu and after glycosylation, the ring opening resulted in free I±-carboxylic acid, which can be directly used to extend the chain to obtain N-glycopeptides. Both the minimum number of steps as well as circumvention of orthogonal protection strategy leads to a cost-effective route for their synthesis. This protocol can be easily scaled up to prepare N-glycosylated Asn/Gln acids in large quantities in fairly good yields. © Georg Thieme Verlag Stuttgart.

The High Stereoselectivity of the Tandem Sequence Diels-Alder Reaction/Ireland­-Claisen Rearrangement Starting from Substituted O-(E)-Buta-1,3-dienyl Ketene Acetals and Cyclic Dienophiles

A new tandem reaction leads to bicyclic cyclohexene derivatives with complete control of the relative configuration of the four chiral centers formed. The high diastereoselectivity is the consequence of an endo-selective Diels-Alder reaction followed by an Ireland-Claisen rearrangement that proceeds via a boat-like transition state. © Georg Thieme Verlag Stuttgart.

Reaction of Benzyne with Styrene Oxide: Insertion of Arynes into a C-O Bond of Epoxides

Benzyne inserts into one of the C-O bonds of styrene oxide to form a dihydrobenzofuran as the major product together with five other reaction products. A detailed study of the reaction mixture clarified an intriguing forty-year-old personal communication from Stiles and Haag. © Georg Thieme Verlag Stuttgart.

α‐EWG‐Substituted Enones: Suitable Substrates for Ring‐Closing Metathesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A Facile Synthesis of Ethyl 2-Acetamido-4-methylenehex-5-enoate, a Versatile Diels-Alder Synthon for the Parallel Synthesis of Novel α-Amino Acid Derivatives

An efficient synthesis of a diene-containing α-amino acid via the use of Denmark's coupling reaction and its application to the synthesis of novel α-amino acid via the Diels-Alder reaction are described. © Georg Thieme Verlag Stuttgart.