Synthetic studies toward the total synthesis of tedanolide: assembly of the C1-C23 carbon backbone

A stereoselective assembly of the C1-C23 fragment representing the carbon backbone of tedanolide was accomplished utilizing a chiral boron reagent to effect the aldol coupling of the C1-C12 diketoester fragment with the C13-C23 aldehyde fragment.     

Spiroleucettadine: synthetic studies and investigations towards structural revision

Synthetic efforts towards spiroleucettadine are described, including the enantioselective synthesis of the presumed biosynthetic precursor. High level density functional theory calculations were used to predict the ¹³C NMR shifts of possible alternative structures and, along with a re-evaluation of the available NMR data, allow the proposal of revised structures for this spirocyclic alkaloid.     

Synthetic studies on apoptolidin: synthesis of the C12-C28 fragment via a highly stereoselective aldol reaction

The stereoselective and convergent synthesis of the C12-C28 segment 2 of the apoptosis inducing macrolide antibiotic, apoptolidin (1), is described. The synthesis involves a highly stereoselective tin(II)-mediated aldol reaction between the C17-C22 ethyl ketone 3 and the C23-C28 aldehyde 4 as the key step.     

Synthetic studies toward potent cytostatic macrolide rhizopodin: stereoselective synthesis of the C16-C28 fragment

A stereoselective synthesis of the C16-C28 fragment of cytostatic C₂-symmetric macrolide rhizopodin is described. Enantioselective addition of a chiral thiazolidinethione derived titanium enolate to acetal, Evans’ aldol reaction, Horner-Wadsworth-Emmons reaction, and Mukaiyama aldol reaction were applied as key steps.     

Synthetic studies on amphidinolides C and F: synthesis of the C18-C29 segment of amphidinolide F

The C18-C29 segment of amphidinolide F is synthesised in 12 steps from 1,4-butanediol. Key steps include a mono-Sharpless dihydroxylation of a dienoate, iodocyclisation to construct the trans-THF ring and an E-selective Wittig reaction to introduce the C25-C26 olefin.     

Studies directed towards the total synthesis of lycoperdinosides: stereoselective construction of the C1-C9 and C10-C21 segments of the molecules

The three chiral centres of the C1-C9 moiety of the six-membered lactone glycosides, lycoperdinosides A and B, have been derived from a common starting material containing a single chiral centre. In contrast, the C10-C21 segment of these molecules has been synthesized using, as key steps, a highly stereoselective aldol reaction, a Ti(III)-mediated opening of a trisubstituted epoxy alcohol and an efficient directed hydrostannylation of a suitably substituted internal alkyne.     

Synthetic studies of cyclic peptides stephanotic acid methyl ester,celogentin C,and moroidin

An account of the total synthesis of stephanotic acid methyl ester and celogentin C is presented. The present synthesis features a tandem asymmetric Michael addition/bromination sequence for the synthesis of leucine-tryptophan moiety, and an oxidative coupling reaction to form the tryptophan-imidazole linkage. Moreover, the total synthesis of moroidin had also been studied, and three different synthetic strategies for the construction of the right-hand ring of moroidin were studied.     

Stereoselective Syntheses of Building Blocks with Three Consecutive Stereogenic Centers: Important Precursors of Polyketide Natural Products [New Synthetic Methods (68)]

Sequences of directly adjacent stereogenic centers were first discovered for the monosaccharides, which therefore constituted the first focus of interest in Stereoselective synthesis. The structures of many polyketide-derived natural products that have been elucidated in recent years often exhibit longer sequences of stereogenic centers in which hydroxy-substituted secondary carbon atoms alternate with tertiary carbon atoms. This finding inspired the development of methods allowing the specific construction of first two and then—more importantly–three neighboring stereogenic centers. The diverse methodologies that have thereby emerged reveal common principles and stress the variety of approaches possible in stereoselective synthesis.     

Synthetic studies towards the novel fomannosane sesquiterpenoid illudosin: framework construction

A synthetic approach to the novel fomannosane sesquiterpene natural product illudosin 2 from the diquinane precursor 5, readily available in turn from commercial 1,5-cyclooctadiene, is delineated. The key steps are the stereoselective construction of the cis, anti, cis-tricyclo[6.2.0.0^2,6]decane system, strategic C-C bond disengagement through Baeyer-Villiger oxidation and functional group adjustments to deliver the carbocyclic core 18 present in the natural product.     

Studies towards the total synthesis of cruentaren A and B: Stereoselective synthesis of fragments C1-C11, C12-C22 and C23-C28

A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn-stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti-stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis-2-butene-1,4-diol respectively.     

Studies directed towards the synthesis of antascomicin A: stereoselective synthesis of the C22-C34 fragment of the molecule

A stereoselective synthesis of the C22-C34 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using d-quinic acid as the starting material and highly stereoselective aldol reactions were employed, as key steps, to build the remaining stereocentres at C23, C26 and C27.     

Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A−F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels–Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D−F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).     

Synthetic studies on goniodomin A: convergent assembly of the C15-C36 segment via palladium-catalyzed organostannane-thioester coupling

A stereocontrolled convergent synthesis of the C15-C36 segment of goniodomin A, a potent anti-angiogenic marine polyether macrolide, has been achieved using Stille-type cross-coupling reaction of a vinylstannane and a thioester as a key segment assembly process.     

Synthetic studies towards crinipellins: construction of the functionalised C20-tetraquinane carbon framework through cationic enone-olefin cyclisation stratagem

A synthesis of 14-epi-crinipellin skeleton, adequately and appropriately functionalised, from a readily available triquinane precursor is described.     

Synthetic studies towards dendridine A: synthesis of hemi-dendridine A acetate by Fischer indolization

A short synthesis of hemi-dendridine A acetate has been accomplished. The synthesis is based on a modified Fischer indolization that represents a rare example of the single-step synthesis of a 7-oxytryptamine from an ortho-oxygenated phenylhydrazine. The synthetic route required developing an efficient synthesis of N-acetyl-2-pyrroline, the key coupling partner for the modified Fischer indolization. Some interesting chemistry associated with the abnormal Fischer indolization has been uncovered, whereby two molecules of the phenylhydrazine substrate combined along the abnormal reaction pathway, affording an unusual N-phenylindoleamine product.     

Synthetic studies of stereocalpin A and its C5-epimer: total synthesis of 11-epi- and 5,11-diepi-stereocalpin A

This Letter describes the synthetic studies of stereocalpin A and its C5-epimer. After various cyclization attempts, successful macrolactamization at 9-10 position was tried inorder to obtain stereocalpin A and its C5-epimer, which were accompanied by complete racemization and resulted in the synthesis of 11-epi- and 5,11-diepi-stereocalpin A. Highly functionalized octanoic acid motif of the depsipeptide was constructed by applying Paterson’s aldol methodology, owing to its diversity in synthesizing various analogs of aliphatic acid.     

Synthetic studies on antascomicin A: construction of the C18-C34 fragment

Stereoselective synthesis of the C18-C34 fragment of antascomicin A is described. Construction of the C27-C34 carbocycle moiety was achieved via catalytic Ferrier carbocylization and Johnson-Claisen rearrangement, which was converted to iodide 2 by use of asymmetric alkylation and Sharpless epoxidation as key transformations. Coupling of iodide 2 and sulfone 3 furnished the C18-C34 fragment.     

Synthetic studies of incednine: synthesis of C1-C13 pentaenoic acid segment

Stereoselective synthesis of the C1-C13 pentaenoic acid segment (4) of the novel antibiotic incednine (1) is described.     

Synthetic studies towards daphniyunnine B: Construction of AC bicyclic skeleton with two vicinal all carbon quaternary stereocenters

The AC bicyclic skeleton of daphniyunnine B with the required two vicinal all carbon quaternary stereocenters (C-5 and C-8) was accomplished in 12 steps from the known cyclohexenol (±)-5.     

Synthetic studies towards anti-SARS agents: application of an indium-mediated allylation of α-aminoaldehydes as the key step towards an intermediate

AG7088 was identified as a good starting point for modification, leading to an efficient and bio-available inhibitor for the SARS coronavirus main proteinase (SARS-CoV M^pro). Synthesis of intermediate 1 and analogues proceeded via a highly diastereoselective indium-mediated allylation of α-aminoaldehydes.