ABSTRACT
(4E,8E,10E)-9-Methyl-4,8,10-sphingatrienine, a core component of marine sphingolipids, was synthesised for the first time using a copper(I)-mediated 1,2-metallate rearrangement of a lithiated glycal as a key step. It was converted to phalluside-1, a cerebroside isolated from the ascidian Phallusia fumigate. By an analogous route, (4E,8E)-9-methyl-4,8-sphingadiene was synthesised and converted to Sch II, a cerebroside that induces fruiting body formation in the basidiomycete Schizophyllum commune.
Subject(s)
Cerebrosides/chemical synthesis , Schizophyllum/chemistry , Urochordata/chemistry , Animals , Cerebrosides/chemistry , Molecular StructureABSTRACT
Caught in the middle: The ionomycin calcium complex (see structure; O red, Ca green) was the target of an approach featuring the efficient asymmetric synthesis of an allene by a copper(I)-mediated anti-selective S(N)2' reaction, a highly stereoselective gold(III)-catalyzed cycloisomerization of an alpha-hydroxyallene, and a Rh-catalyzed rearrangement of an alpha-diazo-beta-hydroxyketone.
Subject(s)
Calcium/chemistry , Ionomycin/chemistry , Anti-Bacterial Agents/chemistry , Catalysis , Cyclization , Gold/chemistry , StereoisomerismABSTRACT
A 1,2-metallate rearrangment of a higher order cuprate derived from an alpha-lithiated xylal derivative and tridecyllithium is the key step in a synthesis of D-erythro-sphingosine and ceramide. A convenient method for preparing alpha-lithiated glycals from alpha-phenylsulfinyl glycals is also described.
Subject(s)
Ceramides/chemical synthesis , Sphingosine/chemical synthesis , Copper/chemistry , Xylose/chemistryABSTRACT
An asymmetric synthesis of the tubulin polymerisation inhibitor (S)-(-)-N-acetylcolchinol is reported based on an intramolecular biaryl oxidative coupling of a 1,3-diarylpropyl acetamide intermediate using phenyliodonium bis(trifluoroacetate) as the final step. Three syntheses of the penultimate 1,3-diarylpropyl acetamide intermediate (S)-(-)-N-[1-[3-(tert-butyldimethylsilyloxy)phenyl)]-3-(3,4,5-trimethoxyphenyl)propyl] acetamide are described which differ in the means by which the stereogenic centre was introduced.
Subject(s)
Colchicine/analogs & derivatives , Acetamides/chemistry , Colchicine/chemical synthesis , Colchicine/chemistry , Crystallography, X-Ray , Molecular Structure , Onium Compounds/chemistry , Oxidation-Reduction , Stereoisomerism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistryABSTRACT
Key steps in the synthesis of the C1-C16 polyketide fragment of ionomycin were the nucleophilic addition of an organocuprate to a neutral (eta3-allyl)iron complex and the construction of a beta-diketone moiety by the Rh-catalysed rearrangement of an alpha-diazo-beta-hydroxyketone.
Subject(s)
Allyl Compounds , Ionomycin/chemistry , Ionomycin/chemical synthesis , Iron , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , StereoisomerismABSTRACT
An enantiospecific synthesis of the phospholipase A(2) inhibitor (+)-(4R)-manoalide is reported in which all 25 carbons of the sesterterpenoid skeleton are constructed from 3-furaldehyde, trimethylalane, oxirane, CO, beta-ionone, and propargyl bromide. The overall yield for the longest linear sequence (12 steps) is 12%. Key steps include (a) a zirconium-catalyzed carboalumination reaction to construct the C10-C11 trisubstituted alkene, (b) a Cu(I)-mediated 1,2-metalate rearrangement to construct the C6-C7 trisubstituted alkene, (c) a Sharpless kinetic resolution to secure the (4R)-stereochemistry, (d) generation of a 5-stannyl-2,3-dihydrofuran by Mo-catalyzed cycloisomerization of a homopropargylic alcohol, and (e) construction of the hydroxyfuranone ring by photooxidation of a silylfuran.
Subject(s)
Alkenes/chemical synthesis , Copper/chemistry , Terpenes/chemical synthesis , Alkenes/analysis , Animals , Catalysis , Cyclization , Kinetics , Magnetic Resonance Spectroscopy , Molecular Structure , Oxidation-Reduction , Porifera/chemistry , Stereoisomerism , Terpenes/analysis , Zirconium/chemistryABSTRACT
The cyclic pentapeptide c(RGDfK), a selective ligand for the alpha(v)beta3 integrin, was synthesised on solid phase. All synthetic operations including the cyclisation step and the appendage of the Bolton-Hunter reagent was conducted on-resin.
Subject(s)
Peptides, Cyclic/chemical synthesis , Cyclization , Integrin alphaVbeta3 , Ligands , Lysine/chemistry , Peptides, Cyclic/pharmacology , Resins, Synthetic/chemistryABSTRACT
Two adjacent stereogenic centres and a pendant alkene were constructed via nucleophilic addition of a 1,3-dioxan-4-ylcopper(I) reagent to a cationic eta3-allylmolybdenum complex as part of a synthesis of (2E,5S,6R,7E)-6-methyl-8-phenylocta-2,7-dienoic acid, a key component of the Cryptophycins. Oxidative addition of Mo(CO)(4)(THF)(2) to allyl benzoates provides an efficient synthesis of eta3-allylmolybdenum(dicarbonyl) complexes.