Catalytic Asymmetric Total Synthesis of Exiguolide.

The catalytic asymmetric total synthesis of (-)-exiguolide, a complex 20-membered macrolide embedded with a bis(tetrahydropyran) motif, is reported. The convergent synthesis involves the construction of the C1-C11 tetrahydropyran segment via catalytic asymmetric allylation and Prins cyclization, and the formation of the C12-C21 phosphonate segment via catalytic asymmetric cyclocondensation reaction and Johnson-Claisen rearrangement. The synthesis of 15-epi-exiguolide is also described.

New entry to the enantioselective formation of substituted cyclohexenes bearing an all-carbon quaternary stereogenic center.

Enantioselective formation of cyclohexene derivatives bearing an all-carbon quaternary stereogenic center is described. The racemic cyclohexenes are readily transformed to chiral substituted cyclohexenes in good yield with excellent enantioselectivity and diastereoselectivity by a palladium-mediated deracemization. The resulting products are promising synthetic intermediates of biologically active natural products. This protocol provides us with a new entry to the concise and scalable synthesis of multifunctionalized compounds.

Total Synthesis of Lajollamycin†B.

The first total synthesis of lajollamycin B, a structurally novel nitro-tetraene spiro-ß-lactone/γ-lactone antibiotic, is described. The convergent synthesis involves the construction of the C8'-C11' nitrodienylstannane and its coupling with the segment prepared from the C1'-C7' ω-iodoheptadienoic acid and the right-hand heterocyclic fragment, which has been utilized for our previous syntheses of oxazolomycin A. The revision of the geometry of the terminal Δ10', 11' -double bond from E to Z is also described for the structure of natural lajollamycin B.

Synthetic Studies on Spirolides A and B: Formation of the Upper Carbon Framework Based on a Lewis Acid Template-Catalyzed Diels-Alder Reaction.

The upper fragment of spirolides A and B, which are marine phycotoxins that exhibit strong antagonistic activities on nicotinic acetylcholine receptors, was constructed. The functionalized cyclohexene in spirolides was stereoselectively synthesized from the bicyclic lactone, which could be readily accessed by the Lewis acid template-catalyzed asymmetric Diels-Alder reaction of the pentadienol and methyl acrylate.

Lewis acid template-catalyzed asymmetric diels-alder reaction.

An asymmetric Diels-Alder reaction of 2,4-dienols and methyl acrylate utilizing a chiral Zn(II)/Mg(II) bimetallic template with low catalyst loading was successfully achieved. The bimetallic Lewis acid template derived from (R)-5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol catalyzed the Diels-Alder reaction in the presence of molecular sieves 4 Što afford various functionalized bicyclic γ-lactones with high enantiomeric purities.

An enantioselective organocatalyzed aza-Morita-Baylis-Hillman reaction of isatin-derived ketimines with acrolein.

A highly enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with acrolein was established using ß-isocupreidine (ß-ICD) or α-isocupreine (α-ICPN) as a chiral acid-base organocatalyst. The present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral tetrasubstituted carbon stereogenic center in up to 98% ee.

Total synthesis of oxazolomycins.

The oxazolomycin family of antibiotics, isolated from several Streptomyces strains, are intriguing molecules for synthesis due to their characteristic oxazole polyene lactam-lactone structures and significant antiviral, antibacterial, and antitumor biological activities. In the last ten years, we have been addressing synthetic problems to accomplish the total syntheses of neooxazolomycin and oxazolomycin A as well as the related antibiotics, inthomycins A, B, and C, which have truncated structures corresponding to the left-hand fragments. This account describes an overview of our synthetic efforts toward these natural products focusing on the strategies and methodologies we devised.

Total synthesis of (-)-dihydrosporothriolide utilizing an indium-mediated Reformatsky-Claisen rearrangement.

The asymmetric synthesis of (-)-dihydrosporothriolide (1), a biologically active bis-γ-butyrolactone, is described, that proceeds through a D-proline-catalyzed asymmetric aminooxylation, indium-mediated Reformatsky-Claisen rearrangement of an α,α-dibromoacetate derivative, and diastereoselective dihydroxylation. The route requires no protective group manipulation and allows the concise seven-step synthesis of 1 from n-octanal.

Total synthesis of biologically active natural products based on highly selective synthetic methodologies.

Total syntheses of structurally and biologically intriguing natural products relying on new synthetic methodologies are described. This article features cinchona alkaloid-catalyzed asymmetric Morita-Baylis-Hillman reactions, heterocycle syntheses based on rhodium-catalyzed C-H amination and indium-catalyzed Conia-ene reactions, and their utilization for the syntheses of the phoslactomycin family of antibiotics, glutamate receptor agonists and antagonists, and alkaloids with characteristic highly substituted pyrrolidinone core structures.

Total synthesis of (-)-ophiodilactone A and (-)-ophiodilactone B.

The first asymmetric total synthesis of (-)-ophiodilactone A and (-)-ophiodilactone B, isolated from the ophiuroid (Ophiocoma scolopendrina), is reported. The key features of the synthesis include the highly stereocontrolled construction of the structurally congested γ-lactone/δ-lactone skeleton through an asymmetric epoxidation, diastereoselective iodolactonization, and intramolecular epoxide-opening with a carboxylic acid, and biomimetic radical cyclization of ophiodilactone A to ophiodilactone B.

Total synthesis of marinomycin A based on a direct dimerization strategy.

The asymmetric total synthesis of (+)-marinomycin A, a 44-membered macrodiolide antitumor agent and antibiotic isolated from a marine actinomycete, Marinispora strain CNQ-140, is reported. The key features of the synthesis include the highly convergent stereocontrolled construction of the monomeric hydroxy salicylate starting from asymmetric epoxidation of the σ-symmetrical dialkenyl carbinol, and an unprecedented direct dimerization through NaHMDS-promoted double transesterification.

α-Isocupreine, an enantiocomplementary catalyst of ß-isocupreidine.

Complementary chemistry! α-Isocupreine (-ICPN) was synthesized for the first time in one step from quinine by treatment with CF3SO3H (see scheme). This compound serves as an enantiocomplementary catalyst to ß-isocupreidine (ß-ICD) in the Morita­Baylis­Hillman reaction.

Total synthesis of (-)-cinatrin C1 based on an In(OTf)3-catalyzed Conia-Ene reaction.

The stereocontrolled total synthesis of (-)-cinatrin C1, a phospholipase A2 inhibitor, has been accomplished. The key feature includes the stereoselective construction of the highly substituted tetrahydrofuran core by In(OTf)3-catalyzed Conia-ene reaction of the oxygen-tethered acetylenic malonic ester followed by dihydroxylation with concomitant lactonization.

Stereocontrolled total synthesis of (-)-englerin A.

The total synthesis of (-)-englerin A, a potent and selective inhibitor of renal cancer cell lines, is described. The key feature includes the stereocontrolled construction of the cyclopentane structure by taking advantage of a base-promoted epoxynitrile cyclization.

Organocatalytic asymmetric syntheses of inthomycins A, B and C.

The total syntheses of (+)-inthomycin A, (+)-inthomycin B and (-)-inthomycin C, the oxazole-triene antibiotics isolated from Streptomyces sp., have been accomplished via the highly enantio- and stereoselective construction of the C1-C7 (iododienyl)aldol units by taking advantage of a Cinchona alkaloid-catalyzed asymmetric ß-lactone synthesis and their isomerisation-free Stille coupling with (E)-5-(3-(tributylstannyl)allyl)oxazole.

A new method for the protection of carboxylic acids with a triisopropylsiloxymethyl group.

An effective method for the protection of carboxylic acids with a triisopropylsiloxymethyl (TIPSOCH(2)) group is described. The reactions of various carboxylic acids with C(12)H(25)SCH(2)OTIPS in the presence of CuBr(2), Et(3)N, and molecular sieves 4A afford the corresponding triisopropylsiloxymethyl esters in good yields.

Recent developments in the Reformatsky-Claisen rearrangement.

The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

Total Synthesis of Thuggacin cmc-A and Its Structure Determination.

The first total synthesis of thuggacin cmc-A and the determination of the absolute structure are described. The thuggacin family of antibiotics is of great interest due to the antibiotic activity against Mycobacterium tuberculosis. Based on the assumption that seven stereogenic centers in thuggacin cmc-A would share the same stereochemistry as thuggacin-A, all stereogenic centers of thuggacin cmc-A were strictly constructed in a stereocontrolled manner. The total synthesis allowed its stereostructure to be fully confirmed.

Formal Synthesis of (-)-Haliclonin A: Stereoselective Construction of an Azabicyclo[3.3.1]nonane Ring System by a Tandem Radical Reaction.

A formal synthesis of (-)-haliclonin A, isolated from the marine sponge Haliclona sp. in Korea, is described. The key feature of the synthesis includes the highly stereoselective tandem radical reaction to construct the azabicyclo[3.3.1]nonane core and the enantioselective formation of an all-carbon quaternary center via the Pd-mediated deracemization.

Asymmetric total synthesis of (+)-phoslactomycin B.

(+)-Phoslactomycin B was synthesized by a highly enantio- and stereoselective approach involving asymmetric pentenylation, Suzuki-Miyaura coupling, ring-closing metathesis, asymmetric dihydroxylation, and Stille coupling. The synthetic method developed enables us to synthesize three other isomers concerning the C11-OH and Delta12-double bond.