A concise synthesis of Tamiflu: third generation route via the Diels-Alder reaction and the Curtius rearrangement

Our third generation synthesis of Tamiflu was achieved in 12 steps from commercially available starting materials, using the Diels-Alder reaction and Curtius rearrangement as key steps.     

A fully stereocontrolled total synthesis of (+)-leucascandrolide A

A highly stereocontrolled total synthesis of leucascandrolide A, a cytotoxic 18-membered macrolide from the calcareous sponge Leucascandra caveolata, starts out with a Jacobsen asymmetric hetero Diels-Alder reaction to configure the 2,6-cis-tetrahydropyran ring. All the remaining oxygenated stereocentres are introduced with high selectivity by relying on substrate-based control. An efficient endgame depends on two Mitsunobu reactions, the first to close the macrolactone with inversion at C17 and the second to attach the oxazole-containing side chain at C5, followed by Lindlar hydrogenation of the two alkynes to provide (+)-leucascandrolide A.     

Enantioselective Iodolactonizations of (E)-and (Z)-5-Substituted-4-pentenoic Acid Derivatives Mediated by Chiral Salen-Co(II) Complex

A number of salen-metal complexes were prepared and their enantioselective catalytic properties toward the asymmetric iodolactonization of (E)-and (Z)-5-substituted-4-pentenoic acid derivatives were investigated. The catalyst system based on salen-Co(II) complex exhibited moderate to good enantioselectivity with the e.e. value ranging from 53% to 74%, as well as high regioselectivity of δ-vs. γ-iodolactones. The salen-Co(II) complex showed the highest enantioselectivity on the asymmetric iodolactonizations ...     

Enantioselective synthesis of 1(R)-hydroxypolygodial

Enantioselective preparation of 1(R)-hydroxypolygodial (5) has been achieved starting from α-ionone through a synthetic strategy involving a Corey-Bakshi-Shibata oxazaborolidine-mediated reduction and a stereoselective Diels-Alder reaction as key steps.     

Enantioselective syntheses of candenatenins B and C using a chiral anthracene auxiliary

The asymmetric syntheses of two anticancer natural products, candenatenins B and C, are described, leading to a revision of the originally assigned stereochemistries. The syntheses follow a Diels-Alder/retro-Diels Alder strategy using a chiral anthracene auxiliary to access both targets with 90% ee. The inherent structural qualities of the auxiliary allow for both regio- and diastereoselective transformations.     

Synthetic studies of GKK1032s: the asymmetric synthesis of the decahydrofluorene skeleton via a novel cyclization of silyl enol ether and sequential retro Diels-Alder and intramolecular Diels-Alder reactions

GKK1032s, which were isolated from the culture broth of Penicillium sp. GKK1032, exhibit antitumor activity. We constructed the fully elaborated decahydrofluorene skeleton of GKK1032s. The C-ring was constructed by intramolecular cyclization reaction between a chiral epoxide and silyl enol ether, and the dienophile moiety was introduced concurrently. In addition, the AB-rings were stereoselectively constructed using novel sequential retro Diels-Alder (DA) and intramolecular Diels-Alder (IMDA) reactions. Several further modifications of the IMDA adduct were carried out, leading to the asymmetric synthesis of the desired hydroxyester including nine stereo centers.     

Enantioselective total synthesis of cis-(+)- and trans-(+)-disparlure

An expedient enantioselective synthetic approach for the gypsy moth sex-attractant pheromone cis-(+)-1 and trans-(+)-disparlure 2 is described employing the optimized combination of organocatalytic MacMillan’s self aldol reaction, Wittig olefination, regioselective ring opening of an epoxide and Mitsunobu esterification reactions as key steps.     

Enantioselective synthesis and absolute configurations of aculeatins A and B

The two naturally occuring, bioactive spiroacetals aculeatins A and B have been synthesized for the first time in enantiopure form using an asymmetric allylation as the only chirality source. A further key step was a stereoselective aldol reaction with remote induction. The absolute configurations of the natural products have been established and the previously assigned relative configurations have been corrected.     

Convenient stereoselective synthesis of some 3-aminosteroid scaffolds

Abstract

An efficient stereoselective synthesis 3α- and 3β-aminoandrostan-17-one and 3α-amino dehydroepiandrosten-17-one based on a Mitsunobu reaction has been developed, using azide as the ammonia equivalent. All the products were isolated in high yield.     

Facile method for the synthesis of oseltamivir phosphate

A ten-step scheme for the preparation of an antiviral agent, ethyl (3R,4R,5S)-4-acetylamino-5-amino-3-(pent-3-yloxy)cyclohex-1-enecarboxylate phosphate, from (-)-shikimic acid was studied. The main parameters of the synthesis were determined and the optimal conditions for the preparation of the intermediate compounds were selected. The total yield of oseltamivir phosphate calculated based on (-)-shikimic acid was 27%.     

Synthesis of aromatic phosphates via cycloaddition of phosphate dienes

Cycloadditions of phosphate dienes and quinones can be used to generate aromatic phosphates. Diethyl 3-methoxy-1-methylene-2-propenyl phosphate shows reactivity, stability, and regioselectivity comparable to the corresponding silyloxy diene. Because the phosphate ester in the product originates in the diene, cycloadditions with quinones will place this ester regiospecifically in the B-ring and allow facile distinction between the B- and A-ring oxygens of the cycloadduct.     

Enantioselective synthesis of Boc-protected norfuranomycins

Garner’s aldehyde is a suitable precursor for the synthesis of both isomers of Boc-protected epi-norfuranomycin. We demonstrate the utility of trisyl chloride as an effective leaving group in the dihydrofuran formation step. We also show that TEMPO/BAIB is an effective oxidant for α-amino alcohols avoiding epimerization of the labile α-proton of the product aldehyde.     

Enantioselective total synthesis of (+)-sarcodictyenone

The first enantioselective total synthesis of (+)-sarcodictyenone is described [4.3% overall yield from (5R,6R)-6-methyl-5-trimethylsily-2-cyclohexenone]. This work establishes the absolute stereochemistry of the natural product.     

(-)-(1R,2S)-肉豆蔻木脂素的不对称合成

报道了天然产物(-)-肉豆蔻木脂素的全合成. 以香草醛为起始原料, 经Wittig反应、LiAlH₄还原和Sharplass不对称双羟化等反应构建了苏式结构的中间体; 以焦性没食子酸为原料, 经Claisen重排反应制得另一种苯丙素片段; 2个中间体通过Mitsunobu反应, 缩合并使构型翻转, 得到赤式-(-)-肉豆蔻木脂素. 为赤式8-O-4′新木脂素的合成提供了一种新方法.     

Enantioselective synthesis of martinelline chiral core and its diastereomer using asymmetric tandem Michael-aldol reaction

The martinelline chiral core 3 and its diastereomer were synthesized by using the asymmetric tandem Michael-aldol reaction as the key step from 4-methoxycarbonylanthranilaldehyde and the α,β-unsaturated aldehyde.     

Enantioselective synthesis induced by chiral organic-inorganic hybrid silsesquioxane in conjunction with asymmetric autocatalysis

5-Pyrimidyl alkanol with up to 96% ee was formed using chiral organic-inorganic hybrid silsesquioxane in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, in conjunction with asymmetric autocatalysis.     

Synthesis of (S)-γ-Lactones with a Combination of Lipase-Catalyzed Resolution and Mitsunobu Reaction

Six kinds of (S)-γ-lactones [e.g., (S)-γ-decalactone, (S)-γ-undecalactone, and (S)-γ-jasmolactone] were synthesized with 71–88% yields and >97% optical purities by combining lipase-catalyzed resolution with the Mitsunobu reaction.     

Enantiospecific synthesis of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A

(−)-(1S,4R)-4-Hydroxy-2-cyclopenten-1-yl acetate provided a convenient entry point for a 12-step chiral preparation of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A.     

Template effects on the asymmetric cycloaddition reaction between 3,4-dimethyl-1-phenylarsole and diphenylvinylphosphine and their arsenic elimination reaction

The organopalladium complex containing ortho-metalated (S)-[1-(dimethylamino)ethyl]naphthalene as the chiral template was employed to promote the asymmetric cycloaddition reaction between 3,4-dimethyl-1-phenylarsole and diphenylvinylphosphine. It has been proven that the chiral template incorporating napthylamine is more efficient than the benzylamine based analogue as evidenced by the drastic improvement in stereoselectivity and reaction rate. However, when no chiral template was employed, trans-[PdI₂(3,4-dimethyl-1-phenylarsole)₂] reacted with trans-[PdI₂(diphenylvinylphosphine)₂] producing a structurally novel diiodo complex, as a result of an interesting selective cleavage of one As-C bond in the norbornene skeleton and subsequent rearrangements within the skeletal framework. The molecular structure of the diiodo product has been confirmed by X-ray crystallography. Structural analysis showed that in addition to the normal As-P five-membered ring, there is one new five-membered ring containing As-O bond being formed during the course of the reaction along with another seven-membered ring incorporating a hydroxy group.