Diastereoselective synthesis of enantiomeric tertiary alcohols via nucleophilic additions to protected D- and L-erythrulose derivatives

The diastereoselectivity of the addition of several organometallic reagents to the carbonyl group of protected - and -erythrulose derivatives has been investigated. Tertiary alcohols are stereoselectively formed, the diastereomeric ratio being markedly dependent on the reagent type, solvent and temperature.     

Halichondrin B: synthesis of a C1-C14 model via desymmetrization of (+)-conduritol E

[reaction: see text] A model C1-C14 segment (1) of halichondrin B was synthesized from (+)-conduritol E (7) in 18 steps and 2.9% overall yield. Key features of the synthesis include the novel ozonolytic desymmetrization of C(2)-symmetric diol 6, the early-stage construction of the C-ring which accompanies installation of the crucial C12 stereocenter, and the use of an enol ether C14-ketone surrogate as a precursor to the CDE-"caged" ketal.     

Total synthesis of (+)-mupirocin H from D-glucose

Enantioselective total synthesis of mupirocin H is accomplished starting from D-glucose featuring strategic application of D-glucose derived chirality, diastereoselective Still-Barrish hydroboration, and further elaboration of carbon chain to furnish a phenyltetrazolyl sulfone intermediate, which on coupling with (2S,3S)-2-methyl-3-(triisopropylsilyloxy)butanal under Julia-Kocienski olefination conditions gave an advanced E-olefinic intermediate selectively. The E-olefin was transformed to the 4-hydroxynitrile, a prefinal substrate, which on acid-catalyzed oxidative lactonization furnished the target molecule mupirocin H in 19 steps from known compound 6 (longest linear sequence) with an overall yield of 4.96%.     

Total stereospecific synthesis of (+) azimic and (+) carpamic acids from D-glucose

The total synthesis of (+)-azimic and (+)-carpamic acids are described, based on a biomimetic heterocyclization of optically active precursors derived from D-glucose.     

Asymmetric total synthesis of (+)-cardiobutanolide via an iterative asymmetric dihydroxylation in PEG

The stereoselective total synthesis of (+)-cardiobutanolide, a polyhydroxylated natural product, is achieved in high yield through Lu and Guo diene synthesis, Sharpless asymmetric dihydroxylation, and one-pot deprotection-lactonization. The utility of a recyclable reagent system in PEG for asymmetric dihydroxylation is demonstrated.     

Diastereoselective synthesis of (+)-nephrosterinic acid and (+)-protolichesterinic acid

A diastereoselective synthesis of (+)-nephrosterinic acid and (+)-protolichesterinic acid, common members of the paraconic acids is described. The synthesis is based on a diastereoselective orthoester Johnson–Claisen rearrangement of a (Z)-allyl alcohol with a vicinal dioxolane moiety as key steps. The synthesis is completed in 10 steps and with overall yields of 15.9% for (+)-nephrosterinic acid and 16.4% for (+)-protolichesterinic acid.     

A novel and enantioselective synthesis of d-(+)-biotin via a Sharpless asymmetric dihydroxylation strategy

A novel and enantioselective synthesis of d-(+)-biotin has been accomplished starting from commercially available cyclohexanone. The key steps in the sequence are the Sharpless asymmetric dihydroxylation of a (E)-ethyl 3-(2-chlorocyclohex-1-en-1-yl)acrylate derivative to establish the stereocenters of d-(+)-biotin, the carboxyalkyl side chain is introduced by unmasking the cyclohexene by ozonolysis and enzymatic hydrolysis of a thioacetate.     

An enantioselective synthesis of (+)-polyoxamic acid via phase-transfer catalytic conjugate addition and asymmetric dihydroxylation

A new enantioselective synthetic method of (+)-polyoxamic acid is reported. (+)-Polyoxamic acid could be obtained in 7 steps with 46% overall yield from diphenylmethyl-glycineimine tert-butyl ester via an enantioselective phase-transfer conjugate addition (99% yield, 96% ee) and an asymmetric dihydroxylation (98% yield, 94% de) as the key reactions.     

Diastereoselective synthesis of fluorinated,seven-membered beta-amino acid derivatives via ring-closing metathesis

[reaction: see text] Cis and trans seven-membered gamma,gamma-difluorinated beta-amino acid derivatives (III) have been prepared with a sequence that starts with imidoyl halides (I), which are condensed with suitable ester enolates to give intermediates (II). These, in turn, can be cyclized by means of a ring-closing olefin metathesis reaction and the product stereoselectively reduced to yield compounds (III) in good overall yields.     

Synthesis of (+)-negamycin from D-glucose

The broad spectrum antibiotic (+)-negamycin (1) was prepared from 1,2-O-isopropylidene-d-glucose (3) in nine steps.     

Diastereoselective synthesis of 1-benzyltetrahydroisoquinoline derivatives from amino acids via 1,4 chirality transfer. Part 1

[structure: see text]. L-(-)-phenylalanine, L-(+)-valine, and L-(-)-proline were used in the diastereoselective synthesis of benzyltetrahydroisoquinoline derivatives.     

Diastereoselective total synthesis of (+)-morusimic acid B, an amino acid from Morus alba

An efficient, flexible and diastereoselective synthesis of the naturally occurring pyrrolidine amino acid, (+)-morusimic acid B, has been accomplished. Starting from chiral, optically active (+)-(3S)-hydroxy butyric acid methyl ester the key steps of our synthesis are diastereoselective α-alkylation of its dianion to introduce the main part of the side chain, Curtius rearrangement of the hydrazide derivative to a 2-oxazolidinone followed by N→π-cyclization with mercury(II) acetate to generate the cis-2,5-disubstituted pyrrolidine ring. The remote C-3 stereocentre is established after chain elongation with the dianion of methyl acetoacetate and asymmetric hydrogenation of the resulting β-oxoester with Noyori's Ru(II)-(R)-BINAP catalyst.     

De novo asymmetric syntheses of D- and L-talose via an iterative dihydroxylation of dienoates

[reaction: see text] A short and highly efficient route to D- and L-talo-gamma-lactones has been developed. The key transformation was the sequential osmium-catalyzed bis-dihydroxylation reaction of substituted 2,4-dienoates. When the first dihydroxylation reaction is performed on (2Z,4E)-dienoates with use of the Sharpless AD-mix procedure, a regio- and enantioselective dihydroxylation resulted along with an in situ lactonization. A subsequent dihydroxylation, using OsO4/NMO in MeOH conditions, resulted in an exceedingly diastereo- and enantioselective synthesis of talo-gamma-lactone.     

Diastereoselective synthesis of 3,3-disubstituted oxindoles from atropisomeric N-aryl oxindole derivatives

Diastereoselective synthesis of 3,3-disubstituted oxindoles has been examined by transformations involving nucleophilic addition, alkylation, and cycloaddition using chiral racemic N-aryl oxindoles bearing C–N axial chirality. The most striking features of this approach are high diastereoselectivities (up to >95:<5) when using ortho-monosubstituted N-aryl oxindoles and easy removal of the p-(benzyloxy)aryl moiety in the axially twisted amides by a mild two-step sequence.     

Diastereoselective synthesis of carbapenams via Kinugasa reaction

A facile approach to carbapenams via Kinugasa reaction between terminal copper acetylides and nonracemic cyclic nitrones derived from malic and tartaric acid is reported. The stereochemical preferences observed in these reactions are explained. The reaction provides an entry to the carbapenams basic skeleton.     

A synthesis of pseudoconhydrine and its epimer via hydroformylation and dihydroxylation

A synthesis of the alkaloid pseudoconhydrine and its epimer has been achieved using tandem hydroformylation-condensation to form the six-membered ring and stereoselective dihydroxylation to introduce oxygenation. The stereoselectivity of dihydroxylation can be explained by lipophilic and electrostatic effects, supported by DFT calculations. The alkaloids can be obtained either by regioselective dehydroxylation or by rearrangement, followed by reduction.     

Diastereoselective nitrenium ion-mediated cyclofunctionalization: total synthesis of (+)-castanospermine

The asymmetric total synthesis of the α-glucosidase inhibitor (+)-castanospermine is reported. The central theme in our approach to this polyhydroxylated alkaloid is the simultaneous generation of the piperidine ring and the C-1/8a erythro stereodiad through the diastereoselective, oxamidation of an unsaturated O-alkyl hydroxamate. This process is believed to proceed sequentially via singlet acylnitrenium and aziridinium ion intermediates.