Stereoselective synthesis of cytoxazone and its analogues

A variety of synthetic routes to (−)-cytoxazone 1, a cytokine modulator isolated from Streptomyces cultures, and its stereomers 2 and regioisomers 3 have been reviewed.     

Stereoselective synthesis of versatile 2-chloromercurium-3,5-syn-dihydroxy esters via intramolecular oxymercuration

Regio- and stereocontrolled alkoxy mercuration of α,β-unsaturated esters allows direct access to 1,3-syn diols in good yields. Demercuration of adducts leads to 1,3 skipped dihydroxy esters, alcohols, and α-halo esters. The deprotection of acetonide with Amberlyst 15 on 1,3-syn-dihydroxy esters gives the corresponding δ-lactones.     

Stereoselective synthesis of 3-azido-2,3-dideoxy-D-ribose derivatives and its utilization for the synthesis of anti-HIV nucleosides

Detail account of the synthesis of 3′-azido nucleosides utilizing 3-azido-2,3-dideoxy-D-ribose derivative 7 as the key intermediate was described. The key intermediate 7 was synthesized from D-mannitol in 8 steps in a preparative scale. The Michael reaction of the azide group with α,β-unsaturated-γ-butyrolactone 4 was affected by the steric bulkiness of the substituent at the 5-O position. A bulky t-butyldiphenylsilyl substitution at 5-O gave almost exclusively the α-azido adduct 5b , while unsubstitution at 5-O produced 1:1 mixture of α-and β-adducts. The ratio of α to β anomers in the condensation between azido acetate 7a and pyrimidine bases for the preparation of AZT and AZDU was greatly influenced by the solvent and the Lewis acid catalyst used. In the synthesis of 12 (AZDU, CS-87), the combination of dichloroethane and trimethylsilyl triflate gave an optimal result, while in the case of 14 (AZT), various conditions gave similar ratio of α,β anomers. The azido intermediate 7b was also utilized for the synthesis of several 3′-azido purine-like nucleosides 16–27 . The glycosylation was also affected by the Lewis acid catalyst. Boron trifluoride etherate gave the desired N₁-glycosylated compounds in which the α-anomer was major, but other catalysts such as trimethylsilyl triflate or stannic chloride produced N₂-glycosylated compounds as the major products. The newly synthesized purine-like compounds have been tested against HIV, however, none of them showed any significant activity.     

Stereoselective total synthesis of protected sulfamisterin and its analogues

The stereoselective synthesis of sulfamisterin I and its unnatural analogues II and V in their protected form was achieved through a common strategy. The Wittig reaction of aldehydes VIII and IX with the C₁₄ hydrophobic side-chain X served as the key C-C connecting transformation. Subsequent functional group inter-conversions in the coupling products XI and XX completed the total synthesis.     

Stereoselective synthesis of (+)-boronolide and its 8-epimer

Starting from readily available carbohydrates the synthesis of 8-epi-(+)-boronolide 19 and (+)-boronolide was achieved with diastereoselective propargylation of alpha-oxygenated aldehyde as a key step.     

Stereoselective synthesis of kurzilactone and determination of its absolute configuration

Both (5S,7S)- and (5R,7S)-isomers of kurzilactone were synthesized from a ‘chiral epoxy-aldehyde synthon’ through the coupling of an acyl anion equivalent and the dianion of acetoacetate, followed by formation of the Kawa-type lactone by cyclization and elimination. Comparing the spectral data of the synthesized and naturally occurring kurzilactone, the C(5)- and C(7)-stereogenic centers of the natural kurzilactone was assigned a corrected anti-relationship with (5R,7S)-absolute configuration.     

Diversity-oriented synthesis of peptide-boronic acids by a versatile building-block approach

A new strategy for the synthesis of peptide-boronic acids (PBAs) is presented. 20 Fmoc-protected natural amino acids with orthogonal side-chain protection were straightforwardly converted into their corresponding boron analogues in three simple steps. Subsequent immobilisation on commercially available 1-glycerol polystyrene resin and on-resin transformations yielded a diversity of sequences in high purity. The strategy eliminates various synthetic obstacles such as multi-step routes, low yields, and inseparable impurities. The described method comprises great potential to be implemented in automated combinatorial approaches by markedly facilitating the access to a variety of PBAs. The coupling of amino acids or other building blocks with α-aminoboronates allows the creation of hybrid molecules with significant potential in various scientific disciplines, such as medicinal chemistry, structural biology, and materials science.

Decarboxylative borylation and monophasic transesterification yields Fmoc-α-aminoboronates for solid-phase peptide synthesis.     

Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach

A highly diastereoselective annulation strategy for the synthesis of alicyclic ketones from diols and pentamethylacetophenone is described. This process is mediated by a commercially available iridium(III) catalyst, and provides efficient access to a wide range of cyclopentane and cyclohexane products with high levels of stereoselectivity. The origins of diastereoselectivity in the annulation reaction have been explored by a series of control experiments, which provides an explanation for how each stereocentre around the newly forged ring is controlled.     

A versatile approach to the reproducible synthesis of functionalized polysiloxane stationary phases

Exploitation of the full potential of selector-modified polysiloxanes as chromatographic stationary phases is limited because conventional methods of silicone synthesis involve strong acids or strong nucleophiles such as water or bases; under these conditions many potentially useful selectors decompose. The general approach to polysiloxane synthesis presented herein gives access to functionalized polysiloxanes under mild conditions. The functional groups incorporated can serve as chromatographic selectors or as electrophilic sites for secondary modification or cross-linking.     

Stereoselective synthesis of C-glycosides from carboxylic acids: the tandem Tebbe-Claisen approach

A variety of beta- or alpha-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. Though of wide scope, for example allowing the synthesis of 1-6 linked C-disaccharides, the methodology does not currently allow the synthesis of C-glycosyl alpha-amino acids.     

Stereoselective total synthesis of preclavulone-A methyl ester and its diastereomer

The total synthesis of preclavulone-A methyl ester and its diastereomer was achieved from same key intermediate in diastereoselective manner. These compounds are recognized as important intermediates in a proposed biosynthesis of marine prostanoids from the Okinawan soft coral, Clavularia viridis, and were recently isolated from the extract of C. viridis by our group.     

Stereoselective synthesis of alkynyl C-2-deoxy-beta-d-ribofuranosides via intramolecular nicholas reaction: A versatile building block for nonnatural C-nucleosides

The reaction of 3,5-di-O-benzyl-2-deoxy-d-ribofuranose with various alkynyllithium reagents afforded diastereomeric mixtures of the corresponding ring-opened alkynyldiols. The resulting diastereomeric mixtures were successively treated with Co(2)(CO)(8), a catalytic amount of TfOH, Et(3)N, and iodine in one pot to give alkynyl C-3,5-di-O-benzyl-2-deoxy-beta-d-ribofuranosides with high beta-selectivities. The cobalt-mediated cyclization (intramolecular Nicholas reaction) is reversible; thus, thermodynamically more stable beta-anomers were obtained preferentially. The alkynyl C-deoxyribofuranosides were converted to a variety of C-deoxyribofuranoside derivatives.     

Stereoselective total synthesis of achaetolide and reconfirmation of its absolute configuration

The stereoselective total synthesis of achaetolide 1 has been achieved and its absolute stereochemistry has been reconfirmed to be 3S,6R,7S,9R configuration. Keck allylation, Sharpless asymmetric dihydroxylation, and ring closing metathesis are the key steps involved in the target synthesis.     

A versatile method for the synthesis of 1,3-metallatitanacyclobutanes

The reaction of Cp₂TiCl₂ with two moles of CH₂(MgBr)₂ gave Cp₂Ti(CH₂MgBr)₂ which with Me₂MCl₂ (M  Si,Ge,Sn) was converted to the corresponding 1,3-metallatitanacyclobutanes.     

Stereoselective synthesis of selenosteroids

A stereoselective synthesis of selenosteroids 4 and 5 has been achieved. Starting from commercial available cholesterol 1, followed by asymmetric epoxidation, and subsequently, by stereoselective epoxide ring opening, employing a selenium nucleophilic species, the correspondent products were afforded in high yields. The compounds were being evaluated for their biological activity and as a chiral pool for asymmetric transformations.     

Stereoselective synthesis of microcarpalide

The first total synthesis of the naturally occurring nonenolide, microcarpalide, is described. The key step in the synthesis was the ring-closing metathesis of a dienic ester prepared in turn by coupling an acid and an alcohol stereoselectively synthesized from (S,S)-tartaric acid and (R)-glycidol, respectively. [structure: see text]     

Stereoselective synthesis of microcarpalide

Microcarpalide is a strong microfilament disrupting agent. The convergent and stereoselective synthesis of microcarpalide was succeeded via Julia olefination and macrolactonization.