A new synthetic approach to the lactol moiety of halichoblelide

A stereoselective approach to the γ-lactol moiety of halichoblelide is described starting from commercially available (R)-3-butyn-2-ol. The key step is the hydroboration of a chiral protected 1,2-butadien-3-ol and its addition to furfural.     

Diels-alder reaction as a synthetic approach to bicyclo[3.3.1]nonane colchicine analogs

Russian Journal of Organic Chemistry -     

Asymmetric synthesis of (+)-L-733,060

A concise, stereocontrolled synthesis of (+)-L-733,060 was achieved. Key features involve diastereoselective oxazoline formation catalyzed by palladium(0) and intramolecular cyclization by catalytic hydrogenation of an oxazoline.     

(+)-MethylCembra-1,3,7,11-tetraene-16-carboxynate的不对称合成研究

The first asymmetric synthesis of ( )-methyl cembra-1,3,7,11-tetraene-16-carboxynate, a naturally occurring cembrane-type macrocyclic diterpene isolated from Sinularia mayi, was achieved via general approach by employing an intramolecular McMurry coupling and Sharpless asymmetric epoxidation as the key steps from readily available starting materials. The synthesis presented here verifies that the absolute configuration of compound 1 was assumed as 15R.     

Facile asymmetric construction of a functionalized dodecahydrobenz[a]indolo[3,2-h]quinolizine template

We report a highly diastereoselective approach for the synthesis of a functionalized dodecahydrobenz[a]indolo[3,2-h]quinolizine ring system that is present as the heterocyclic core of the manadomanzamine alkaloids. We have achieved complete control over the relative and absolute stereochemistries at the three contiguous stereocentres at ring positions 1, 10 and 24 in only two linear synthetic steps. The introduction of useful functionality to the heterocyclic skeleton is significant as this may allow for future derivatization, and application of this route in an asymmetric synthesis of the manadomanzamine natural products.     

A short approach to the bicyclo[4.3.0]nonane fragment of stawamycin

The bicyclo[4.3.0]nonane (C₁₁-C₂₁) fragment of stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(−)-3-hydroxy-2-methylpropionate. Key steps are a Pd-catalysed Stille coupling reaction between a vinyl iodide and a vinyl stannane followed by an intramolecular Diels-Alder cycloaddition reaction to give the desired adduct as the major isomer in 21% overall yield.     

A novel approach to the Taxol A-ring synthetic equivalents

A novel short approach to the A-ring synthetic equivalents of Taxol was described. Oxabicyclic ketone 3 served as a versatile template for selective functionalization leading to oxabicyclic vinylic ether 6 in two steps, which was hydrolyzed under mild acidic conditions to afford the hydroxy aldehyde derivative 7. Synthetic equivalents 2 of Taxol A-ring were thus, accessible from hydroxy aldehyde 7.     

Diastereoselective approach to trans-5-hydroxy-6-substitutedethanone-2-piperidinones: Scalable syntheses of (+)-febrifugine and (+)-halofuginone

An efficient diastereoselective approach to access trans-5-hydroxy-6-substitutedethanone-2-piperidinones skeleton has been developed through sequential addition-deprotection-cyclization process involving aldimine 6 with substituted acetones. The diastereoselectivity of substitution at C-6 position of 2-piperidinone was controlled by α-siloxyl group and chiral sulfinamide moiety. In addition, the utility of this effective approach is demonstrated by the scalable syntheses of (+)-febrifugine (2) and (+)-halofuginone (4).     

Asymmetric synthesis of 3(S),17-dihydroxytanshinone

The first synthesis of 3(S),17-dihydroxytanshinone was achieved by ultrasound promoted Diels-Alder reaction of the protected 3-hydroxymethyl-4,5-benzofurandione with a vinylcyclohexene derivative. Bioassay showed that the synthetic 3(S),17-dihydroxytanshinone was active in vitro against HL-60 tumor cell line by MTT method.     

Synthesis of adamantane and bicyclo[3.3.1]nonane derivatives with the oxetane moiety

A method of synthesis of 3-hydroxyoxetane esters with adamantane- and bicyclo[3.3.1]nonane-containing carboxylic acids is reported.     

A concise approach to 2-azabicyclo[3.3.1]nonane derivatives from an acyclic precursor

[Reaction: see text]. Condensation of a readily available 5-amino-2-alkenoate ester with alpha-unsubstituted aliphatic aldehydes leads to substituted 1,2,3,4-tetrahydropyridines. Subsequent manipulation of the ester and enamine functions gives a quick access to 2-azabicyclo[3.3.1]nonane-containing compounds.     

Asymmetric synthesis of furofurans

Furofurans are one of the largest sub-types of classical lignans which have been found to possess a broad range of important biological activities. Tremendous efforts have been directed to develop synthetic methodologies for the synthesis of furofurans, especially in a stereoselective manner, due to their interesting bioactivities associated with the structural and stereochemical complexity. This article summarizes the reports on asymmetric synthesis of furofurans disclosed during the period of 2004–2017.     

Asymmetric synthetic access to the hetisine alkaloids: total synthesis of (+)-nominine

A dual cycloaddition strategy for the synthesis of the hetisine alkaloids has been developed, illustrated by a concise asymmetric total synthesis of (+)-nominine (7). The approach relies on an early-stage intramolecular 1,3-dipolar cycloaddition of a 4-oxido-isoquinolinium betaine dipole with an ene-nitrile dipolarophile. Subsequent late-stage pyrrolidine-induced dienamine isomerization/Diels-Alder cascade allows for rapid construction of the carbon--nitrogen polycyclic skeleton within this class of C(20)-diterpenoid alkaloids.     

Total synthesis of (+)-eupomatilone 2 via asymmetric [2,3]-Wittig rearrangement of highly oxygenated biphenylmethyl ethers

We have achieved the total synthesis of (±)- and (+)-eupomatilone 2 isolated from the Australian shrub Eupomatia bennettii. The key reaction was an asymmetric [2,3]-Wittig rearrangement employing a bis(oxazoline) chiral ligand. Although the highly oxygenated biphenylmethyl ether exhibited considerably lowered enantioselectivity as compared with the non-substituted biphenylmethyl ether, the selectivity was improved to 89% ee by using n-BuLi and ether as the base and the co-solvent, respectively.     

Synthetic approach to preparation of indole derivatives fused with a bicyclo[3.3.1]nonane framework

Starting with Δ¹⁵-17-ketosteroids, applying Normant reaction with allylmagnesium bromide and anionic Cope rearrangement of the formed allyl alcohol, 15α-derivatives of androstane series were prepared. The latter were brought into Wittig reaction with an ylide generated from ethyltriphenylphosphonium bromide, and the product was subjected to ene reaction to provide 15α-substituted pregnanes.     

A Diels-Alder approach to trans-trisbicyclo[2.2.1]heptabenzene derivative

A new route to the synthesis of a trans-tris(bicyclo[2.2.1]hexeno)benzene derivative, using Diels-Alder reaction as critical step, was investigated. The compound with six methoxycarbonyl groups was successfully synthesized in good yield without any organometallic reagents. Some useful by-products from dimethyl but-2-ynedioate were also isolated from the last step. Perhaps due to stereo-hindrance or electrostatic repulsion in the cis-isomer, trans-isomer was found to be the only isomer in the crystal and its structure was proved by X-ray diffraction.     

Asymmetric approach towards the total synthesis of (+)-actinopyllic acid

This paper describes our efforts towards the asymmetric total synthesis of (+)-actinophyllic acid. Starting from the chiral oxazolidinone 9, an azocino [4,3-b]indolyl intermediate (5) possessing the A/B/C ring system and the C16 quaternary stereogenic center of actinophyllic acid has been synthesized. Key steps include a LHMDS-promoted condensation to establish the critical C2–C16 bond and a successive four-step transformation to assemble the eight-membered C-ring of the target molecule.     

Asymmetric Michael addition reactions catalyzed by a novel upper-rim functionalized calix[4]squaramide organocatalyst

A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated carbonyl compounds in high yields (up to 99 %) and good to excellent enantiomeric excesses (up to 99% ee). The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions. Moreover, this strategy also provides valuable and easy access to chiral chromene, naphthoquinone and acetylacetone derivatives, which are important skeletons in biological and pharmaceutical compounds.     

Asymmetric Michael addition reactions catalyzed by a novel upper-rim functionalized calix[4]squaramide organocatalyst

A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated carbonyl compounds in high yields (up to 99 %) and good to excellent enantiomeric excesses (up to 99% ee). The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions. Moreover, this strategy also provides valuable and easy access to chiral chromene, naphthoquinone and acetylacetone derivatives, which are important skeletons in biological and pharmaceutical compounds.     

New approach toward the total synthesis of (+)-aphidicolin by tandem transannular Diels-Alder/aldol strategy

The synthesis of a 15-membered macrocyclic triene containing all the required substituents of ring A of (+)-aphidicolin (1) is reported. This compound underwent a thermal transannular cycloaddition followed by an intramolecular aldol reaction to yield tetracycle 32 containing 8 chiral centers which is considered a key intermediate for the synthesis of (+)-aphidicolin and related analogs.