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In the first comprehensive biological assessment of the tambjamine class of marine alkaloids, synthetically derived samples of compounds 1-9 have been subjected to evaluation as antimicrobial agents and screened for their cytotoxic effects on various human cancer cell lines. Most were strongly active against the fungus Malassezia furfur (>amphotericin B) and showed considerable, but non-selective, antiproliferative activity against both human cancer and normal cell lines. Tambjamines I and J (6 and 7, resp.) displayed significant apoptosis-inducing effects.

The title alkaloids, (−)-1, (−)-2, (−)-4 and (+)-5 respectively, have each been prepared from the enantiomerically enriched (74% ee) tetrahydroindolizine 14 which is itself obtained via an organocatalyzed and enantioselective intramolecular Michael addition reaction of the pyrrole 13 incorporating an N-tethered and β,β-disubstituted acrylaldehyde moiety.

RANEY® cobalt, which was first prepared in the 1930s, is known to function effectively as a catalyst for certain chemoselective reductions. However, its utility in chemical synthesis does not seem to have been fully appreciated. This first comprehensive survey of the literature on chemical transformations involving RANEY® cobalt attempts to redress matters by, among other things, highlighting the differences between the performance of this system and its much more well-known but usually less selective congener RANEY® nickel. A reliable method for preparing consistently effective RANEY® cobalt is presented together with a protocol that avoids the need to use it with high pressures of dihydrogen. As such, it is hoped more attention will now be accorded to the title reagent that offers considerable promise as a powerful tool for chemical synthesis, particularly in the assembly of polycyclic frameworks through tandem reductive cyclisation processes.

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Although sulfated xylooligosaccharides are promising therapeutic leads for a multitude of afflictions, the structural complexity and heterogeneity of commercially deployed forms (e. g. Pentosan polysulfate 1) complicates their path to further clinical development. We describe herein the synthesis of the largest homogeneous persulfated xylooligomers prepared to date, comprising up to eight xylose residues, as standards for biological studies. Near quantitative sulfation was accomplished using a remarkably mild and operationally simple protocol which avoids the need for high temperatures and a large excess of the sulfating reagent. Moreover, the sulfated xylooligomer standards so obtained enabled definitive identification of a pyridinium contaminant in a sample of a commercially prepared Pentosan drug and provided significant insights into the conformational preferences of the constituent persulfated monosaccharide residues. As the spatial distribution of sulfates is a key determinant of the binding of sulfated oligosaccharides to endogenous targets, these findings have broad implications for the advancement of Pentosan‐based treatments.

The non-natural enantiomeric forms of narciclasine and lycoricidine ((-)-1 and (-)-2, respectively), as well as congeners 3-6 are available through chemoenzymatic synthesis. Accordingly, they have now been tested for their cytotoxic effects in a 13-member human cancer cell-line panel and found to be only weakly active. In contrast, an authentic sample of the natural enantiomeric form of narciclasine ((+)-1) was found to be highly active in the same screens.

Dedicated to Professor Albert Eschenmoser in recognition of his seminal contributions to so many aspects of chemistry and chemical biologyAbstract: The cis-1,2-dihydrocatechols 5-7, which are obtained in high yield and ca. 99.8% ee by microbial oxidation of the corresponding aromatic compound, have been converted, via reaction sequences involving three distinct types of one-carbon deletion processes, into the four D-aldopentoses.The D-aldopentoses 1-4 and their derivatives are of considerable interest as starting materials for chemical synthesis, 1 as building blocks in the construction of carbohydrate-based drugs 2 and as probes of various biochemical processes. 3 Consequently, new methods for the preparation of differentially protected and/or isotopically labelled forms of these compounds should prove valuable. The capacity to prepare such five-carbon sugars, especially 17 O-, 13 C-and/or 2 H-labelled variants, 4 could be greatly facilitated by using appropriate non-carbohydrate based starting materials. 4b,5 However, in contrast to the considerable effort that has been devoted to the synthesis of various pentitols 6 and the aldohexoses, 7 much of which exploits asymmetric epoxidation chemistry, examples of the preparation of the aldopentoses from non-carbohydrate sources remain rather limited. 3c,8 In an important contribution to the general area, Hudlicky et al. 9 have demonstrated that the enantiopure six-carbon cis-1,2-dihydrocatechol 5 can be converted into L-ribono-g-lactone acetonide. The key steps involved initial ozonolysis, which deletes two carbons, followed by Wittig olefination chemistry to reinstate one carbon. It is against such a background that we now wish to report carbon-atom efficient syntheses of the title compounds from the cis-1,2-dihydrocatechols 5-7 which are themselves readily obtained in large quantity and high enantiomeric excess by microbial oxidation of the corresponding halobenzene. 10,11 Scheme 1 Reagents and conditions: (i) see ref. 12; (ii) see ref. 12; (iii) TBDMSCl (2.95 mole equiv.), Hünig's base (3.8 mole equiv.), DMF, 18 °C, 8 h; (iv) ozone (excess), MeOH, -78 °C, 10 min., then NaBH 3 CN (ca. 6.0 mole equiv.), HCl (2 M in MeOH), 0 to 18 °C, ca. 2.5 h; (v) DIBALH (2.5 mole equiv.), CH 2 Cl 2 , -78 °C, 2 h then quench with MeOH; (vi) 4:1 v/v TFA/H 2 O, 18 °C, 18 h.A concise synthesis of D-lyxose (2) from compound 5 is shown in Scheme 1 and involves initial conversion of the starting material into the corresponding acetonide 8. 12 This derivative undergoes a b-face selective reaction with singlet-oxygen and the resulting endoperoxide is immediately cleaved with thiourea to give the previously reported 12 g-hydroxyenone 9 (ca. 38% from 5). In the key step of the reaction sequence, the readily derived tert-butyldimethylsilyl (TBDMS)-ether, 10 {80%, m.p. < 50 °C (lit. 12 m.p. = 50-54 °C), [a] D = -74 (c 5.5) 13 }, of compound 9 was subjected to ozonolytic cleavage followed by a reductive "work-up" using sodium cyanoborohydride at pH 3. 14 In this way the lactone 11 {82%, m.p. ...