Synthesis of tertiary carbinamines

An efficient synthesis of tertiary carbinamines using a one-pot, three-component reaction employing TMSCl activation of an intermediate imine salt followed by addition of an organometallic is described. An optimized second generation chiral synthesis of select tertiary carbinamines utilizing the Ellman sulfinamine was subsequently developed on a multi-gram scale and is also described.     

Preparation of 3,3-disubstituted oxindoles by addition of malonates to 3-halo-3-oxindoles

A method for the synthesis of 3,3-disubstituted oxindole derivatives is described. This involves the base-mediated addition of malonate esters to 3-halo-3-alkyloxindoles. The addition is tolerant of a range of alkyl substituents at position 3 of the oxindole. Addition to an aryl chloro-oxindole is also described.     

Metabolites of microorganisms. 130. Synthesis of delta-N-hydroxy-L-arginine

A synthesis of the antibiotically active amino acid, δ-N-hydroxy-L -arginine, starting from L -ornithine is described. In addition a new synthesis of δ-N-hydroxy-L -ornithine, an important building stone of many sideramines, is given.     

Synthesis of isoquinuclidinones via a tandem amination/imination sequence: application to the synthesis of (−)-mearsine

The facile synthesis of a range of novel isoquinuclidinones from 6-acyl-cyclohex-2-enones is described, employing aqueous ammonia in a one-pot procedure involving initial conjugate addition of ammonia followed by cyclisation via intramolecular imine formation. The scope and limitations of the methodology are described as is an efficient synthesis of the Elaeocarpus alkaloid (−)-mearsine.     

Formal synthesis of (+)-crocacin C

The formal synthesis of (+)-crocacin C is reported. The approach described takes advantage of a highly regioselective epoxide cuprate addition and a diastereoselective Overman rearrangement. The synthesis is practical and amenable to scale up.     

Synthesis of substituted imidazoles via organocatalysis

A one-pot synthesis of substituted imidazoles is described. The cornerstone of this methodology involves the thiazolium-catalyzed addition of an aldehyde to an acyl imine to generate the corresponding alpha-ketoamide in situ followed by ring closure to the imidazole in a one-pot sequence. The extension of this methodology to the one-pot synthesis of substituted oxazoles and thiazoles is also described. [reaction: see text]     

Synthesis of toxyloxanthone B

A synthesis of the naturally occurring xanthone toxyloxanthone B is described, in which the key step is the regioselective addition of a methyl salicylate to a substituted benzyne, followed by cyclization of the intermediate aryl anion to form the xanthone, the regiochemistry of the aryne addition being confirmed by X-ray crystallography. Subsequent introduction of the pyran ring by [3,3]-rearrangement and deprotection completed the synthesis.     

Total synthesis of the polyenoyltetramic acid polycephalin C

The total synthesis of the polyenoyltetramic acid polycephalin C is described. Key steps of the synthesis include a double Swern oxidation, double Takai reaction and a double Stille reaction. In addition, the absolute stereochemistry of the ring junction has been determined by synthesis of both isomers and comparison of their CD spectra with natural polycephalin C.     

Total synthesis of (±)-chamobtusin A

The total synthesis of chamobtusin A, the first diterpenoid alkaloid isolated from the whole Pinales, is described. Key features of the synthesis include a stereoselective intramolecular Michael addition to install a key stereocenter and an oxidative manipulation to prepare a 2H-pyrrole ring.     

Total synthesis of RK-397

An enantioselective synthesis of the polyene macrolide RK-397 is described. The use of the same eight-carbon building block twice for the construction of the polyol chain allowed for a highly convergent synthesis. The synthesis highlights stereoselective vinylogous aldol addition using a chiral bisphosphoramide as well as a sequential palladium-catalyzed cross-coupling reaction for the preparation of key fragments.     

Michael addition of ortho-lithiated aryloxiranes to alpha,beta-unsaturated malonates: synthesis of tetrahydroindenofuranones

A short and efficient synthesis of tetrahydroindenofuranones based on the Michael addition of ortho-lithiated aryloxiranes to alkylidene malonates followed by the nucleophilic oxirane ring-opening and subsequent lactonization is described. The methodology has been applied to the synthesis of a structural analogue of epipodophyllotoxins.     

Stereoselective synthesis of the C1-C10 fragment of rhizoxin D

A novel approach towards the synthesis of the C1-C10 fragment of the biologically active antimitotic agent rhizoxin D is described. The synthesis involves a stereoselective Michael addition reaction of lithium diallyl cuprate with an α,β-unsaturated six membered lactone.     

Stereoselective synthesis of a tetrahydropyranyl diarylheptanoid,ent-diospongin A

The stereoselective synthesis of the unnatural enantiomer of a cyclic diarylheptanoid, diospongin A is described. The salient feature of this synthesis is the formation of a tetrahydropyran ring via the AgOTf-catalysed intramolecular oxa-Michael addition of a β-hydroxy ynone followed by hydrogenation     

Triptycene as a rigid, 120° orienting, three-pronged, covalent scaffold for porphyrin arrays

The synthesis of novel porphyrin trimers covalently linked by one central, rigid triptycene unit is described. Reaction of 2,6,14-triiodotriptycene, generated in a three-step synthesis from triptycene, with borylated porphyrins under Suzuki cross-coupling conditions afforded porphyrin trimers. In addition, Sonogashira cross-coupling conditions could be successfully applied for the synthesis of trimeric porphyrin arrays as well.     

Progress toward synthesis of diazonamide A. Preparation of a 3-(oxazol-5-yl)-4-trifluoromethyl-sulfonyloxyindole and its use in biaryl coupling reactions

[formula: see text] The synthesis of a 3-oxazol-5-yl-indole-4-triflate is described, featuring a Sch?lkopf reaction to prepare the oxazole. In addition, the participation of this intermediate in biaryl coupling reactions toward the total synthesis of the natural product diazonamide A is presented.     

Solid-phase synthesis of oxazolones and other heterocycles via Wang resin-bound diazocarbonyls

The preparation of Wang resin bound α-diazo-β-ketoesters is described. These highly useful intermediates were used for the synthesis of a series of heterocycle libraries, which were obtained from the resin using TFA cleavage. In addition, a novel route for the synthesis of oxazolones using an N-H insertion strategy is disclosed.     

Total synthesis of the duocarmycins

The total synthesis of (+)-duocarmycin A and SA through a common indoline intermediate is described. The key reactions include selective lithiation of a 2,6-dibromoiodobenzene derivative and diastereoselective addition to a chiral nitroalkene, copper-mediated aryl amination, and addition of aryllithium to azlactones.     

An approach to the skeleton of the securinega alkaloids. The total synthesis of (+/-)-securinine

[structure: see text]. The concise total synthesis of securinine in nine steps from readily available starting materials is described. Key steps of the synthesis include an addition of a silyloxyfuran to an in situ generated iminium ion and a novel ring closing metathesis reaction.     

Synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses

The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses is described. The sequence involves an addition of PhSeCF₂TMS to carbohydrate-derived aldehydes followed by a radical cyclization, and provides a secure strategy for a future synthesis of pentofuranoses and nucleoside analogues.     

Concise, Biomimetic Total Synthesis of d,l-Marcfortine C

A biomimetic total synthesis of the fungal metabolite marcfortine C utilizing an intramolecular Diels-Alder reaction is described. In addition, a key stereoselective oxaziridine-mediated oxidation/pinacol rearrangement of indole 24 was used to complete the total synthesis.