Synthesis of the liposidomycin diazepanone nucleoside

[structure: see text] The synthesis of the liposidomycin degradation product 4 from D-glucose establishes its stereochemistry as 5'S,6'S and, by incorporation of the earlier diazepanone relative stereochemical assignment, establishes the absolute stereochemistry of the liposidomycins 1 and 2 as 5'S,6'S,2'S,3'S.     

Assignment of stereochemistry to cyclohexenylidenecyanoacetates by 1H NMR spectroscopy

The stereochemistry of various pairs of isomeric 2-cyclohexen-1-ylidenecyanoacetates was assigned using ¹H NMR spectroscopy. The isomers with the γ-methylene or the γ-vinyl protons cis to the carbalkoxy group were found to have the signals of these protons at approximately 0.3 ppm and 1 ppm, respectively, downfield relative to their geometrical isomers or the corresponding 2-cyclohexen-1-ylidenemalononitriles. The observation regarding the γ-vinyl proton proved useful for the assignment of configuration to cyclohex-enylidenecyanoacetates derived form cholest-4-en-3-one. The large and constant downfield shift (c. 1 ppm) of the γ-vinyl proton when cis to the ester group results from the rigid cyclohexenylidenecyanoacetate system, in which the vinylic proton can approach more closely to the magnetically anisotropic ester carbonyl group.     

Assignment of absolute stereochemistry and total synthesis of (-)-spongidepsin

[structure: see text] An enantioselective total synthesis of (-)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis.     

Synthetic studies towards diazepanone scaffolds

The synthesis of new enantiopure polyfunctionalised diazepanone scaffolds is described. The key steps involve the opening of an azido-epoxide C4 building block derived from l-ascorbic or d-isoascorbic acid by a l-serine derivative followed by a lactonisation–lactamisation two-step sequence.     

Efficient synthesis of polyfunctionalised enantiopure diazepanone scaffolds

The synthesis of polyfunctionalised enantiopure 1,4-diazepan-3-one scaffolds from l-serine derivatives and azidoepoxides readily available from either l-ascorbic or d-isoascorbic acid, allowing access to various configurations at chiral centres, is described. The key steps are the nucleophilic opening of the epoxide by the amine of serine followed by a lactonisation-lactamisation sequence.     

A convergent synthetic approach to the nucleoside-type liposidomycin antibiotics

[reaction: see text] A synthetic approach toward the liposidomycins, a family of complex nucleoside-type antibiotics, is reported based on the synthesis of epoxy-amides derived from the reaction of sulfur ylides with the uridyl aldehyde derivative 6. To this end, the epoxy-amide derivative of indoline 14 was stereoselectively prepared and, after treatment with DDQ, transformed into the corresponding N-indole epoxyamide 15. The indole 15 provides ready access to a variety of structures related to the diazepanone core present in the liposidomycins by reaction with a variety of amines.     

New unsymmetrically substituted tetrahydrofurofuran lignans from artemisia absinthium : Assignment of the relative stereochemistry by lanthanide induced chemical shifts

The isolation of thirteen tetrahydrofurofuran lignans from the roots of A. absinthium and six closely related species is reported. A new group of four lignans, all stereoisomers of 1- [(3,4-methylenedioxy-5-methoxy) phenyl]-4-(3,4,5-trimethoxyphenyl)-tetrahydro-1H,3H-furo[3,4-c]furan, was found. The compounds, named sesartemin, episesartemin A, episesartemin B, and diasesartemin, were characterized by ¹H NMR (including lanthanide induced shifts), UV, IR and MS. A fifth new lignan of the sesamin type (the eq/eq isomer of fargesin) could be identified as a minor constituent. The relative configurations of two further products (fargesin and epiashantin) could be confirmed by the lanthanide induced shift technique.     

On the stereochemistry of the aldol-addition

NOE-experiments and STO-3G calculations suggest that E-enol borates exist in an U-conformation $\text{7a}$, whereas the Z-enol borates should prefer the extended conformation $\text{8b}$. These observations have been linked to the stereoselectivity of the aldol addition. The resulting predictions are in line with the stereoselectivity observed on addition of cyclohexenol borates to benzaldehyde.     

On the stereochemistry of palmerolide A

Degradative studies of the anticancer macrolide palmerolide A have resulted in re-assignment of the C-7, C-10, and C-11 stereocenters.     

On the stereochemistry of the bis-nor-wieland-miescher ketome

The chemo- and stereoselective reduction and the absolute configuration of 5-methylbicyclo[3.3.0]oct-1-en-3,6-dione is reported.     

On the stereochemistry of the Pictet-Spengler reaction

A pathway for the Pictet-Spengler reaction is proposed herein, which is consistent with all of the known mechanistic and sterochemical observations concerning the formation of tetrahydro-β-carbolines by this method.     

The stereochemistry of ketoreduction

In this issue of Chemistry & Biology, Leadlay and coworkers report overproduction of a number of ketoreductase domains from modular polyketide synthases. These discrete enzymes allow the stereochemistry of polyketide ketoreduction to be studied in isolation.     

Reinvestigation of the stereochemistry of kulokekahilide-2

An attempt to carry out a total synthesis of kulokekahilide-2 (1) by macrolactonization of a seco acid prepared from a suitably protected hexapeptide and a dioxy acid moiety unexpectedly resulted in the formation of the 43-epimer (1a) of the cytotoxic depsipeptide, for which structure 1b has previously been proposed. A second attempt involving macrolactamization of the corresponding amino acid gave the target product, 1b, but the spectral data of the product did not match those of natural 1. Furthermore, neither 1a nor 1b showed any cytotoxicity, from which it is concluded that the structure of natural 1 is incorrect and should be re-examined.     

The stereochemistry of heterocycles

Fifteen previously unreported 2-alkyl- and 5-alkyl-2, 2-dimethyl-1, 3-dithianes have been synthesized by the condensation of 2-alkylpropane-1, 3-dithiols with acetaldehyde, isobutylraldehyde, and acetone, and their structures have been confirmed by their IR spectra. The existence of stereoisomers in a number of the thioacetals has been shown by GLC and TLC. Some of the stereoisomeric 2, 5-diakyl-1, 3-dithianes have been separated by fractionation in an efficient column into the individual isomers, the purity of which was confirmed by TLC, GLC, and IR spectroscopy.For part III, see [11].     

Chiral stereochemistry of nanoparticles

The whole array of organic and inorganic nanoparticles, from fullerenes and carbon nanotubes to metals and metal oxides, is discussed in terms of chirality and its stereochemical consequences on the basis of the unified “core-shell” concept.