Total synthesis and stereochemical reassignment of (+)-dolastatin 19, a cytotoxic marine macrolide isolated from Dolabella auricularia

Using conformational analysis and biogenetic considerations, a revised configurational assignment for the cytotoxic marine macrolide dolastatin 19 is proposed, together with its validation by completion of the first total synthesis. Key features of the highly stereocontrolled route include an asymmetric vinylogous Mukaiyama aldol reaction to simultaneously install both the remote C13 stereocenter and the C10-C11 (E)-trisubstituted olefin, two sequential 1,4-syn boron-mediated aldol reactions, and a late-stage, α-selective Mukaiyama glycosylation to append the l-rhamnose-derived pyranoside.     

Stereochemical determination of dictyostatin, a novel microtubule-stabilising macrolide from the marine sponge Corallistidae sp

The relative stereochemistry of the 22-membered marine macrolide dictyostatin, a Taxol-like antimitotic agent, was determined based on a combination of extensive high field NMR studies, including J-based configuration analysis, and molecular modelling.     

Exiguolide, a new macrolide from the marine sponge Geodia exigua

A new 20-membered macrolide designated exiguolide has been isolated from the marine sponge Geodia exigua, and its structure determined by interpretation of spectroscopic data. Exiguolide specifically inhibited fertilization of sea urchin (Hemicentrotus pulcherrimus) gametes but not embryogenesis of the fertilized egg.     

Total synthesis of (-)-dictyostatin

A convergent total synthesis of dictyostatin is described. Key features of the synthesis include the use of titanium-mediated cyclizations of (silyloxy)enynes for the synthesis of stereotriads, a subunit coupling by metathesis, and macrocyclization by intramolecular Horner-Wadsworth-Emmons olefination.     

Total synthesis of (−)-centrolobine

Stereoselective synthesis of (−)-centrolobine, an anti-Leishmania agent, was accomplished via an intramolecular Barbier-type reaction of iodo-ester with n- or t-butyllithium followed by Lewis acid-promoted Et₃SiH reduction of the resulting hemiacetal.     

A facile approach to the synthesis of securinega alkaloids: stereoselective total synthesis of (−)-allonorsecurinine

A concise stereoselective total synthesis of alkaloid (−)-allonorsecurinine is described utilizing classical reactions such as Grignard, Aldol and Horner-Wittig reactions as the key steps.     

Total synthesis of (−)-baconipyrone C

A highly stereoselective asymmetric total synthesis of marine polypropionate (−)-baconipyrone C has been achieved. Utilization of desymmetrization technique to create five stereogenic centres, Sharpless epoxidation, Gilman's reaction and resolution of methyl group using enzyme PS-C is the highlight of the synthesis.     

Total synthesis of (+)-epiepoformin and (−)-phyllostine

An efficient asymmetric total synthesis of naturally occurring cyclohexeneoxides, (+)-epiepoformin and (−)-phyllostine has been achieved using the chiral building block available from the base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone. Since (−)-theobroxide was derived from the same precursor of (+)-epiepoformin, the formal total synthesis of (−)-theobroxide has also been achieved.     

Total synthesis of potential antitumor agent, (-)-dictyostatin

[structure: see text] The potential antitumor agent (-)-dictyostatin has been synthesized utilizing Brown crotylboration to achieve eight of the eleven chiral centers. The yield for the 26-step longest sequence is approximately 4%. The C9-C10 coupling is achieved via a stereoselective vinylzincate addition.     

Total synthesis of halipeptin A, a potent anti-inflammatory cyclodepsipeptide from a marine sponge

Total synthesis of halipeptin A, a potent anti-inflammatory cyclodepsipeptide, was achieved through proline-catalyzed asymmetric α-oxidation, diastereoselective aldol reaction, silver cyanide-mediated esterification, and macrolactamization.     

An improved synthesis of (−)-brevisamide, a marine monocyclic ether amide of dinoflagellate origin

An improved synthesis of (−)-brevisamide a marine cyclic ether isolated from the red-tide dinoflagellate Karenia brevis was achieved. The ether ring portion was constructed from an unsaturated lactone, which was prepared enantioselectively via an Evans aldol reaction and one-pot lactonization in the presence of excessive base after an Ando reaction. The ether ring and a dienol side chain fragment were connected via Suzuki-Miyaura coupling.     

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.     

A stereocontrolled approach for the synthesis of 2,5-diaryl-3,4-disubstituted furano lignans through a highly diastereoselective aldol condensation of an ester enolate with an α-chiral center: total syntheses of (−)-talaumidin and (−)-virgatusin

A general stereocontrolled approach for entry into a family of highly biologically active 2,5-diaryl-3,4-disubstituted furano lignans has been developed. The key step involves a diastereoselective aldol-type condensation of an ester enolate having an α-chiral center with an aromatic aldehyde. The methodology has been illustrated with the total syntheses of (−)-talaumidin and (−)-virgatusin.     

Total synthesis of (−)-incarvilline

An enantioselective synthesis of (−)-incarvilline is presented, employing a three-component coupling reaction and an intramolecular enone-olefin [2+2] photocycloaddition followed by a SmI₂-induced cyclobutane ring-opening reaction.     

Total synthesis of (−)-muricatacin

A total synthesis of (−)-muricatacin has been achieved using a commercially available starting material and our furan approach to oxacyclic systems, the proven scope of which is thus broadened.     

Total synthesis of (−)-xanthatin

The first enantioselective total synthesis of xanthatin, a xanthanolide sesquiterpenoid exhibiting potent antibacterial activity against MRSA, has been accomplished from an optically pure bicyclic lactone, previously synthesized by our group.     

Total synthesis of (−)-cleistenolide

The total synthesis of (−)-cleistenolide, a novel natural product recently isolated from the annonaceae species cleistochlamys kirkii oliver, is described. The synthesis proceeds starting from easily accessible d-manitol using a selective benzoylation, a selective acetonide deprotection, silylprotection and ring-closing metathesis reaction.     

Stereoselective synthesis of (−)-allosedamine

A stereoselective synthesis of (−)-allosedamine is disclosed. β-Aminosulfoxide 4 was generated stereoselectively by condensation of the sulfinyl anion 2 with N-Ts imine 3. The bromohydrin 5 was obtained by intramolecular sulfinyl group participation and the piperidine ring of allosedamine was elaborated using the ring-closing metathesis (RCM) reaction.