Biomimetic synthesis of the shimalactones

A biomimetic synthesis of shimalactone A and B is described. Its key features are an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a Stille coupling/8pi-6pi electrocyclization cascade to create the oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis is convergent and void of protecting groups.     

Rapid synthesis of the N-methylwelwitindolinone skeleton

An efficient, convergent synthesis of the core bicyclo[4.3.1]decane ring system of welwitindolinones is described. Key steps in the synthesis include an intramolecular palladium-catalyzed enolate arylation reaction to create the desired bicyclic skeleton and a Curtius rearrangement to install the bridgehead isocyanate unit. [reaction: see text]     

Metathesis reactions for the synthesis of ring-fused carbazoles

[reactions: see text] The metathesis reaction is used as a key step for the synthesis of the indolo[2,3-a]carbazole core of rebeccamycin 13 and the sulfur analog of furostifoline 21. Using the same methodology for the attempted synthesis of furostifoline, we unexpectedly formed tert-butyl-2a-methyl-1,2,2a,10c-tetrahydro-6H-cyclobuta[c]furo[3,2-a]carbazole-6-carboxylate 26 from the unstable diene, tert-butyl 2-(2-isopropenyl-3-furyl)-3-vinyl-1H-indole-1-carboxylate 25, presumably via a spontaneous pi8 electrocyclization reaction.     

On the synthesis of protopine alkaloids

For the synthesis of protopine alkaloids, we studied a reaction sequence based on a ring enlargement of indeno[2,1-a][3]benzazepines by a singlet oxygen oxygenation, followed by conversion of an amide carbonyl group of the resultant 10-membered keto-lactam to a methylene group, which is the last step for completion of the synthesis. The key substances, indeno[2,1-a][3]benzazepines, were prepared by Bischler-Napieralski cyclization of alkoxy-substituted 1-(2-bromobenzyl)-3-benzazepin-2-ones. Steric effects of the substituents in this synthesis were examined.     

Studies towards the synthesis of the benzodiazepine alkaloid auranthine

Different approaches towards the synthesis of auranthine have been investigated. A completed synthesis of 3‐[2‐(4‐oxo‐3,4‐dihydro‐quinazolin‐2‐yl)‐3,4‐dihydro‐1H‐benzo[e][1,4]‐diazepine‐2,5‐dione, an auranthine precursor, which after dehydration with 50% propylphophonic acid anhydride solution in ethl acetate and DMA gave a C‐acetyl derivative of aurnathine. Additionally studies towards the synthesis of fused quinazolinones yielded the C‐acetylated pyrido[2,1‐b]quinazolinones or butyric acid derivatives.     

Total synthesis of pyridovericin: studies toward the biomimetic synthesis of pyridomacrolidin

[reaction: see text] The total synthesis of the novel metabolite pyridovericin 1 is reported. The synthesis of this key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily available 2,4-dihydroxypyridine.     

Total synthesis of (+)-cyanthiwigin U

A concise total synthesis of the tricyclic terpene cyanthiwigin U has been accomplished in 12 steps and 17% overall yield. The key step of the synthesis is a two-directional tandem metathesis reaction that forms the cyclohepta[e]indene core from a readily available bicyclo[2.2.2]octene.     

Practical synthesis of new functionalized tetraphenylenes

The practical synthesis procedure of substituted tetraphenylene derivatives involving the synthesis of a precursor for 4, 7-dunethoxyisobenzofuran and Diets-Alder addition of 4, 7-dimethoxyisobenzofuran generated in situ to 5, 6, 11,12-te-tradehydrodibenzo[a,e]cyclooctene, followed by a low valent titanium mediated deoxygenation to give 1,4, 11, 14-tetra-methoxy-dibenzo[b, n] tetraphenylene, which can be further demethyiated to the corresponding phenolic compound, which was acetylated to afford 1,4,11,14-tetraacetoxy-dibenzo-[ b, n] tetraphenylene.     

Traceless solid-phase synthesis of heterosteroid framework

[reaction: see text]A traceless solid-phase synthesis of cyclopenta[c]-4H-chromen-8-ol, benzo[d]cyclopenta[e]-3H-3-azin-8-ol, and other 11-heterosteroids via the fulvene hetero [6 + 3] cycloaddition is described.     

Ring-expansion approaches for the total synthesis of salimabromide

We describe the evolution of a synthetic strategy for the construction of the marine polyketide salimabromide. Combining a bicyclo[3.1.0]hexan-2-one ring-expansion to build up a functionalized naphthalene and an unprecedented rearrangement/cyclization cascade, enabled synthesis of a dearomatized tricyclic subunit of the target compound. Alternatively, an intramolecular keteniminium [2 + 2]-cycloaddition and subsequent Baeyer–Villiger ring-expansion gave access to the sterically encumbered architecture of salimabromide. Sequential oxidation of the carbon framework finally enabled the total synthesis of this unusual natural product.     

Total synthesis of vibriobactin

The first synthesis of the natural product N-[3-(2,3-dihydroxy-benzamido) propyl]-1,3-bis[2-(2,3-dihydroxyphenyl)-$\text{trans}$-5-methyl-2-oxazoline-4-carboxamido] propane (vibriobactin) is described. The synthesis illustrates the problems and solutions involved in the asymmetric functionalization of norspermidine, a triamine which consists of a symmetrical methylene backbone. Finally, the synthesis provides an independent and definitive proof of Neiland's suggested structure of vibriobactin.     

Total synthesis of the Kopsia lapidilecta alkaloid (+/-)-lapidilectine B

The total synthesis of Kopsia lapidilecta alkaloid (+/-)-lapidilectine B is described. Notable elements of this synthesis include the first natural products application of the Smalley azido-enolate cyclization to form the 1,2-dihydro-3H-indol-3-one (indoxyl) core and installation of the pyrrolidine ring by a 2-azaallyllithium [3+2] cycloaddition with the acetylene equivalent phenyl vinyl sulfide. Closure of the eight-membered perhydroazocine ring is accomplished via the intramolecular S(N)2 substitution of a mesylate. This constitutes the first synthesis of a member of the 5,6,12,13-tetrahydro-11a,13a-ethano-3H-pyrrolo[1',2':1,8]azocino[5,4-b]indole class of alkaloids.     

Total synthesis of sordaricin

[structure: see text] The total synthesis of sordaricin, the diterpene aglycone of an important class of antifungal compounds, is described. Two approaches were explored, the first of which utilized a possible biogenetic intramolecular [4 + 2] cycloaddition to form the complete carbon skeleton of the target molecule. A second approach using a tandem cycloreversion/intramolecular [4 + 2] cycloaddition sequence is also detailed.     

The synthesis of dinaphthothiophenes

The synthesis of dinaphtho[1,2-b:2′,3′-d]thiophene ( 6 ), dinaphtho[2,1-b:2′,3′-d]thiophene ( 15 ), dinaphtho-[1,2-b:1′,2′-d]thiophene ( 20 ), dinaphtho[2,1-b:1′,2′-d]thiophene ( 26 ), dinaphtho[2,3-b:2′,3′-d]thiophene ( 37 ) and dinaphtho[1,2-b:2′,1′-d]thiophene ( 45 ) has been accomplished.     

Formal synthesis of (+/-)-peduncularine: use of the

[reaction: see text] The formal synthesis of the alkaloid (+/-)-peduncularine (1) was accomplished through the use of a [3 + 2] allylic silane annulation. The annulation of cyclohexadienyl silane 6 with chlorosulfonyl isocyanate followed by an in situ reduction provided bicyclic lactam 7. Conversion of this intermediate to 2 in three steps completed the formal synthesis of (+/-)-peduncularine.     

Total synthesis of (+)-sundiversifolide

The first, enantiocontrolled total synthesis of (+)-sundiversifolide has been accomplished using the sequential ring-closing metathesis, [3,3]-sigmatropic rearrangement, and iodolactonization for the key assembly of the cis-fused oxabicyclo[5.3.0]decene framework of the natural product. [structure: see text]     

Asymmetric total synthesis of batzelladine D

[formula: see text] The first enantioselective total synthesis of a batzelladine alkaloid is described. The central reaction in the synthesis of (-)-batzelladine D (2) is a tethered Biginelli condensation of a guanidine aldehyde and an acetoacetic ester to generate a 7-substituted-1-iminohexahydropyrrolo-[1,2-c]pyrimidine intermediate having the anti stereochemistry of the methine hydrogens flanking the pyrrolidine nitrogen.     

Alkaloid synthesis using 2nd generation palladium-catalyzed cycloalkenylation. Diastereoselective total synthesis of α-skytanthine

An efficient approach to the synthesis of 3-azabicyclo[3.3.0]octanes and 3-azabicyclo[4.3.0]nonanes by 2nd generation palladium-catalyzed cycloalkenylation is described. Additionally, this reaction is used for the diastereoselective total synthesis of (±)-α-skytanthine.     

Natural product synthesis via the polybromo ketone-iron carbonyl reaction

Application of the polybromo ketone-iron carbonyl reaction to natural product synthesis is summarized. The general synthesis of tropane alkaloids has been achieved via the reductive [3+4] cyclocoupling of sym-tetrabromoacetone with N-methoxycarbonylpyrrole as the key step. Ready availability of 8-oxabicyclo[3.2.1]oct-6-en-3-one from the tetrabromoacetone and furan has opened a new, efficient entry to natural C-nucleosides including pscudouridine, pseudocytidinc, and showdomycin. The artificial analogues such as 2-thiopscudouridine, 6-azapseudouridine, pseudoisocytidine, etc., are also obtainable. The oxabicyclic ketones bearing an isopropyl substituent at the appropriate position serve as intermediates for the synthesis of naturally occurring troponoids, nezukone, α-thujaplicin, and hinokitiol (β-thujaplicin). Carbocamphenilone and camphenic acid have been prepared through the [3 + 4] reaction of 1,1,3-tribromo- 3-methylbutan-2-one and cyclopentadiene. The [3+2] cyclocondensation of an α,?a-dibromo ketone and a styrene derivative leads to the single-step synthesis of α-cuparenone. 1,3-Dibromo-3,7-dimethyloct-6-en-2- one derived from nerol (or geraniol) undergoes the biogenctic-type double cyclization. The iron carbonylassisted intramolecular [3 + 2] cyclocoupling gives camphor accompanied by other monoterpenic ketones. A mixture of campherenone and epicampherenone has been obtained from related dibromo ketone prepared from farnesols. The hetero [3+2] reaction by use of dibromo ketones and N,N-dimethylcarboxamides, forming 3 (2H)-furanones, is employable for the preparation of muscarine alkaloid derivatives.     

Model studies toward the total synthesis of the Lycopodium alkaloid spirolucidine

[reaction: see text] A strategy for the synthesis of the spirocyclic core of spirolucidine was explored through a model study. The diene 4a was prepared and photolyzed to give the desired [2 + 2] photoadduct 17 containing the correct relative stereochemistry corresponding to spirolucidine.