One good ring deserves another: A highly efficient and stereoselective cycloisomerization of α‐thioallenes to 2,5‐dihydrothiophenes is the first example of a gold‐catalyzed carbon–sulfur bond formation (see scheme, X=Cl, I). Both gold(I) and gold(III) salts can be used as the precatalyst, with AuCl and AuI giving the best yields. The method is of interest for the stereoselective synthesis of biologically active 2,5‐disubstituted dihydro‐ or tetrahydrothiophenes.

No abstract

The gold‐catalyzed cycloisomerization of various α‐aminoallenes affords the corresponding 3‐pyrrolines in good to high chemical yields and – if the amino group is unprotected – with complete axis‐to‐center chirality transfer. Diminished levels of chirality transfer were observed in cases of N‐protected substrates, which may be the result of partial epimerization of the allene in the presence of the gold precatalyst. The low reactivity of the intramolecular hydroamination of unprotected α‐aminoallenes with AuCl3 was improved by use of gold(I) halides as the precatalyst. Mechanistic studies suggest that a gold(I) compound (formed by oxidation of the aminoallene) is the catalytically active species even if the reaction is started with a gold(III) precatalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A 78-year-old woman is described who presented with a diaphragmatic hernia through the foramen of Morgagni. A definitive diagnosis was confirmed by a sagittal view on magnetic resonance imaging prior to surgery. The hernia was repaired laparoscopically under an abdominal wall lifting technique without pneumoperitoneum, and her symptoms completely resolved postoperatively with no evidence of recurrence. The laparoscopic repair was considered a suitable and safe procedure for the treatment of a Morgagni hernia.

We reported previously that the abnormally augmented expression of connexin 26 (Cx26) is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells, and that the exogenous expression of a dominant negative form of Cx26 inhibits the spontaneous metastasis of BL6. Here we show that daily intraperitoneal (i.p.) injections of oleamide, a sleep-inducing lipid hormone, weakly inhibited the spontaneous metastasis of BL6 cells. To obtain a more effective reagent, 19 oleamide derivatives were chemically synthesized and tested for their ability to inhibit the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of Cx26 or Cx43. One of these, denoted metastasis inhibitor-18 (MI-18), inhibited the GJIC formed by Cx26 as well as oleamide but unlike oleamide, which is a non-selective inhibitor of connexin, it did not inhibit the GJIC formed by Cx43. Daily i.p. injections of MI-18 potently blocked the spontaneous metastasis of BL6 cells down to 15% of that in the untreated control mice. MI-18 was safe because even after >7 weeks of daily injections, the survival rate of the mice was 93%. We propose that MI-18 may serve as a novel and clinically important prototype of a potent inhibitor of spontaneous metastasis.

The total syntheses of tetrapeptides tubulysins D (1 b), U (1 c), and V (1 d), which are potent tubulin polymerization inhibitors, are described. The synthesis of Tuv (2), an unusual amino acid constituent of tubulysins, includes an 1,3-dipolar cycloaddition reaction of chiral nitrone D-6 derived from D-gulose with N-acryloyl camphor sultam (-)-9 employing the double asymmetric induction, whereas the synthesis of Tup (20), another unusual amino acid, involves a stereoselective Evans aldol reaction of (Z)-boron enolate generated from (S)-4-isopropyl-3-propionyl-2-oxazolidinone with N-protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins U (1 c) and V (1 d) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for γ-amido alcohol functionality. Furthermore, to understand the structure-activity relationship of tubulysins, we synthesized tubulysin D (1 b) and cyclo-tubulysin D (1 e) from 2-Me and 20, and ent-tubulysin D (ent-1 d) from ent-2-Me and ent-20, respectively. The preliminary results regarding their biological activities are also reported.

Gold verbindet: Die hocheffiziente, stereoselektive Cycloisomerisierung von α‐Thioallenen zu 2,5‐Dihydrothiophenen ist das erste Beispiel für eine goldkatalysierte C‐S‐Bindungsknüpfung. Als Präkatalysator können Gold(I)‐ und Gold(III)‐Salze verwendet werden, wobei AuCl und AuI die besten Ausbeuten ergeben (siehe Schema; X=Cl, I). Die Methode ist interessant für die stereoselektive Synthese biologisch aktiver 2,5‐disubstituierter Dihydro‐ oder Tetrahydrothiophene.

The first total synthesis of the proposed structure of phaeosphaeride A has been achieved via six-membered-ring formation by means of an intramolecular vinyl-anion aldol reaction as the key step. This synthesis suggests a revised configurational assignment for phaeosphaeride A.