A new stereocontrolled synthetic route to (-)-echinosporin from D-glucose via Padwa allenylsulfone [3 + 2]-anionic cycloadditive elimination

A new formal total synthesis of (-)-echinosporin has been developed based upon the Padwa [3 + 2]-cycloadditive elimination reaction of allenylsulfone 4 with the D-glucose-derived enone 14 which provides cycloadduct 12.     

A general route to protected quaternary alpha-amino acids from beta-amino alcohols via a stereocontrolled radical approach

A radical-based approach facilitates the highly stereocontrolled functionalisation of beta-amino alcohols, opening up a new, generally applicable methodology for the preparation of quaternary alpha-amino acids.     

Synthesis of pachastrissamine from phytosphingosine: a comparison of cyclic sulfate vs an epoxide intermediate in cyclization

[reaction: see text] The syntheses of the cytotoxic natural product pachastrissamine and its unnatural 4-epi-congener were accomplished starting from a natural phytosphingosine. The relatively unstrained cyclic sulfate intermediate smoothly underwent the 5-endo cyclization to yield the 2,3,4-trisubstituted tetrahydrofuran ring system of pachastrissamine. The corresponding epoxy alcohol afforded the 4-epi-congener via a tosylate-mediated double inversion process.     

Efficient synthesis of D-erythro-sphingosine and D-erythro-azidosphingosine from D-ribo-phytosphingosine via a cyclic sulfate intermediate

The synthesis of naturally occurring d-erythro-sphingosine and synthetically useful D-erythro-2-azidosphingosine from commercially available d-ribo-phytosphingosine is described. An important feature of this synthesis is the selective transformation of the 3,4-vicinal diol of phytosphingosine into the characteristic E-allylic alcohol of sphingosine via a cyclic sulfate intermediate.     

Stereoselective preparation of ceramide and its skeleton backbone modified analogues via cyclic thionocarbonate intermediates derived by catalytic asymmetric dihydroxylation of alpha,beta-unsaturated ester precursors

A novel and efficient synthetic route to ceramide 1a and skeleton backbone modified ceramide analogues 1b,c is reported. The syntheses utilize osmium-catalyzed asymmetric dihydroxylation of (E)-alpha, beta-unsaturated ester 5a-c as the chiral induction step, with the desired configurations in the products 1a-c, 2a, and 13 being generated by regioselective azide substitution at the alpha position of alpha,beta-dihydroxyesters 6a-c via a cyclic thionocarbonate intermediate. Azido esters 10a-c are converted to the corresponding ceramides 1a-c by a sequence of azide reduction, N-acylation, ester reduction (NaBH(4)/LiBr), and Birch reduction of the triple bond (Li, EtNH(2)). These seven- to eight-step syntheses afford the target compounds 1a-c with excellent stereocontrol and in 30-42% overall yields. Furthermore, propargylic alpha-azido-beta-hydroxyester 10a is converted to D-erythro-sphingosine 2a via simultaneous reduction of the triple bond, azido, and ester functional groups with LiAlH(4), providing a highly concise and practical four-step synthesis of this key naturally occurring sphingolipid. The L-erythro stereoisomers are also available in high enantiomeric purity by the method described herein.     

Synthesis of bioactive indolocarbazoles: synthesis, nucleophilic ring-opening and chiral base desymmetrisation of a cyclic sulfate intermediate

A number of new functionalised bridged indolocarbazole systems have been prepared by ring-opening reactions of a key cyclic sulfate intermediate, prepared from the corresponding diol by the action of sulfuryl diimidazole and DBU. The same cyclic sulfate also undergoes an unprecedented asymmetric rearrangement to a chiral ketone, on treatment with a chiral lithium amide base.     

Deoligomerization: a new route to lactams from unsaturated amides via radical oligomerization

[reaction: see text] Triethylborane-initiated atom transfer radical oligomerization of N-allyl or N-(3-butenyl)iodoacetamides followed by treatment with hydrochloric acid and subsequent neutralization with K(2)CO(3) led to the formation of the corresponding 5-hydroxyl-substituted delta-lactams or caprolactams, respectively. This oligomerization-deoligomerization sequence serves as an alternative to the corresponding intramolecular cyclization reactions.     

A practical and efficient synthetic route to stable zirconocene-ate zwitterionic complexes

The reaction of α-zirconated phosphorus compounds 6 and 10 with methyl propiolate or dimethylacetylene dicarboxylate gives rise to stable zwitterionic zirconocene-ate complexes 7, 8, 11 and 12 in which the zirconium atom is linked exclusively to carbon atoms.     

C-glycosylmethylene carbenes: synthesis of anhydro-aldose tosylhydrazones as precursors; generation and a new synthetic route to exo-glycals

Acylated anhydro-aldononitriles (glycosyl cyanides) were transformed into anhydro-aldose tosylhydrazones by Raney-nickel reduction in the presence of tosylhydrazine in a one-pot reaction. The configuration of the C=N double bond in these hydrazones was E as proven by 15N-1H coupling constants as well as X-ray crystallography. Thermolysis in refluxing 1,4-dioxane of the sodium salts of the tosylhydrazones obtained by sodium hydride (generally 10 eq.) resulted in the formation of anhydro-1-deoxy-ald-1-enitols (exo-glycals). "Dimeric" N-glycosylmethyl anhydro-aldose tosylhydrazones could also be isolated when the use of less base caused incomplete deprotonation of the starting compounds. This two-step procedure constitutes a novel, reasonably short synthetic pathway to acylated exo-glycals from the readily available glycosyl cyanides.     

A general and efficient route to enantioselective synthesis of pumiliotoxin A alkaloids via a common key intermediate

A general and efficient formal synthesis of pumiliotoxins and allopumiliotoxins has been achieved via a common key intermediate 3a. Our route featured a novel one-pot substitution-ring-opening sequence and an efficient Claisen-type condensation. This method is also applicable to quinolizidine derivative 2b.     

Facile transformation of 2-azetidinones to unsaturated ketones: application to the formal synthesis of sphingosine and phytosphingosine

2-Azetidinones were smoothly transformed to unsaturated ketones through the ring opening of activated 2-azetidinone by phosphonate stabilized carbanion and subsequent Horner–Wadsworth–Emmons olefination of the resulting β-ketophosphonates with aldehydes. A formal synthesis of l-erythro-sphingosine and d-lyxo-phytosphingosine from readily available 2-azetidinone was established utilizing this methodology.     

A highly stereocontrolled and efficient synthesis of α- and β-pseudouridines

A five-step practical and stereocontrolled synthesis of α- and β-pseudouridines from d-ribonolactone is described. The key step involves a highly stereoselective reduction of a hemiketal C-nucleoside intermediate in each case. Multi-gram quantities of β-pseudouridine can now be made available.     

A new synthetic route to the synthesis of nordasycarpidone derivatives

A new synthetic route for the synthesis of the nordasycarpidone derivative 11 which has hexahydro‐1,5‐methanoazocino[4,3‐b]indol skeleton, is described. Construction of the tetracyclic structure was achieved by catalytic reduction and cyclization reaction of the nitrile derivative. Also many new tetrahydrocarbazole derivatives ( 4, 5, 6, 7, 8, 9 ) and a dasycarpidol derivative ( 10 ) were synthesized.     

Palladium-catalyzed stereocontrolled cyclization of 1,3-diene monoepoxide: A route to a new synthetic intermediate for de-ab-cholestane derivative.

The optically active (2R, 3R)-3-[(3R)-(E)-Benzyloxymethoxy-5-methyl-1-hexenyl]-2-(3-butenyl)-2-methyl-1-cyclopentanone (8) was synthesized as a precursor of vitamin D₃(5) by palladium-catalyzed syn-S_N2′ cyclization of [Z,Z(22S, 23R)]-ene oxide 6 as a key reaction.     

A simple and efficient synthesis of functionalized cyclic carbonate monomers using a versatile pentafluorophenyl ester intermediate

An improved two-step synthetic route to functionalized cyclic carbonate monomers that features a novel cyclic carbonate intermediate with an active pentafluorophenyl ester group (MTC-OPhF(5)) has been developed. The versatile pentafluorophenyl ester intermediate can be synthesized on the gram to kilogram scale in one high-yielding step and is easy to store and handle on the benchtop. The active pentafluorophenyl ester of MTC-OPhF(5) is amenable to further substitution with suitable nucleophiles such as alcohols and amines to generate functionalized cyclic carbonates in high yields. The substitution reaction is tolerant of a wide variety of functionalities, including various hydrophobic and hydrophilic groups, reactive functionalities (via thiol-ene click chemistry or alkyl halides), and protected acids, alcohols, thiols, and amines. In view of the ever-increasing need for biodegradable and biocompatible polymers, this new methodology provides a simple and versatile platform for the synthesis of new and innovative materials.     

An efficient preparation of isosteric phosphonate analogues of sphingolipids by opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated alkylphosphonic esters

D-erythro-(2S,3R,4E)-Sphingosine-1-phosphonate (1), the isosteric phosphonate analogue of naturally occurring sphingosine 1-phosphate (1a), and D-ribo-phytosphingosine 1-phosphonate (2), the isosteric phosphonate analogue of D-ribo-phytosphingosine-1-phosphate (2a), were synthesized starting with methyl 2,3-O-isopropylidene-d-glycerate (4) and D-ribo-phytosphingosine (3), respectively. Oxirane 12 was formed in eight steps from 4, and cyclic sulfamidate 22 was formed in five steps from 3. The phosphonate group was introduced via regioselective ring-opening reactions of oxirane 12 and cyclic sulfamidate 22 with lithium dialkyl methylphosphonate, affording 13 and 23, respectively. The synthesis of 1 was completed by S(N)2 displacement of chloromesylate intermediate 14b with azide ion, followed by conversion of the resulting azido group to a NHBoc group and deprotection. The synthesis of 2 was completed by cleavage of the acetal, N-benzyl, and alkyl phosphonate ester groups.     

A new and efficient synthetic route toward 3,4-alkylenedioxypyrrole (XDOP) derivatives via Mitsunobu chemistry

A new and high yielding synthetic route toward 3,4-alkylenedioxy-functionalized pyrroles has been achieved by performing tandem Mitsunobu reactions on diethyl 1-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylate using a variety of 1,2-alkanediols or 1,3-alkanediols.     

A novel and highly efficient synthetic route to unsymmetrical organoselenides using cesium bases

A new and convenient one-pot method for the preparation of unsymmetrical selenides has been developed. In the presence of cesium hydroxide, molecular sieves, and DMF, benzeneselenol undergoes direct alkylation with various alkyl halides for the synthesis of alkyl phenyl selenides in moderate to excellent yields. Another method to prepare unsymmetrical organoselenides was also completed by coupling terminal alkynes with benzeneselenyl bromide. As an application, the synthesis of a selenopeptide was also accomplished. Furthermore, this methodology was extended to the synthesis of an organoselenide on solid support.