Concise synthesis of complicated polypropionates through one-pot dissymmetrical two-directional chain elongation

Herein, a major breakthrough in a sulfur dioxide-mediated oxyallylation cascade reaction is reported that allows the preparation of complex long-chain polyketide fragments with more than ten stereogenic centers through a carefully designed desymmetrization process. An allylbissilane is combined, under the appropriate reaction conditions, with two different 1,3-dioxy-1,3-dienes permitting the construction of a 13-membered polypropionate precursor in one pot. Four stereocenters are selectively created during this process. The so-obtained pseudo-C(2)- or -C(S)-symmetric products are desymmetrized through selective deprotection and can be selectively elongated in both directions using aldol chemistry.     

Enantioselective total synthesis of marine diterpenoid clavulactone

The key steps in the synthesis of clavulactone are formation of an enantiopure cyclopentane precursor by epoxide rearrangement and intramolecular carbonyl-ene reaction, construction of the 3,4-dihydro-2H-pyran ring by intermolecular hetero-Diels-Alder reaction, closure of the eleven-membered ring, and finally generation of the lactone functionality by chemoselective allylic C(sp(3))-H oxidation.     

Total synthesis of 7-ethyl-10-hydroxycamptothecin (SN38) and its application to the development of C18-functionalized camptothecin derivatives

A new chemical synthesis of SN38, the active metabolite of the camptothecin prodrug irinotecan, has been achieved in 12 steps from simple, commercially available starting materials. A mild and efficient FeCl₃‐catalyzed Friedländer condensation was successfully applied to construct the AB ring system. Functionalization of the C ring was accomplished by a vinylogous Mukaiyama reaction of an in situ generated N‐acyliminium intermediate with a silyl enol ether. An intramolecular oxa Diels–Alder reaction efficiently constructed the D and E rings in one step. Successive asymmetric dihydroxylation and I₂‐based hemiacetal oxidation furnished the stereochemistry of SN38 with high enantiopurity. Utilizing the ABC‐ring intermediate and a functionalized silyl enol ether permitted the synthesis of a number of new C18‐functionalized SN38 derivatives. Several of the novel SN38 derivatives that bore a C10 methoxy group were found to exhibit comparable or more potent inhibitory activity against the proliferation of cancer cells relative to SN38.     

Iterative deoxypropionate synthesis based on a copper-mediated directed allylic substitution: formal total synthesis of borrelidin (C3-C11 fragment)

A new iterative strategy for the flexible preparation of any oligodeoxypropionate stereoisomer is presented which relies on an o-DPPB-directed copper mediated allylic substitution employing enantiomerically pure Grignard reagents; the reaction is working with perfect control over all aspects of the reaction selectivity. This key C--C bond-forming step features reversed polarity compared with established enolate alkylation methodology. It thus avoids existing problems of enolate alkylation strategies such as enolate reactivity as well as costs and problems associated with the chiral auxiliary. Practicability of this new method is demonstrated through application in natural product syntheses. Thus, an efficient synthesis of the northern part of the angiogenesis inhibitor borrelidin (28), the deoxypropionate building block 27, could be devised, representing a formal total synthesis.     

Iriomoteolide-1b中C(13)-C(23)片段的立体选择性合成

采用已知文献报道的化合物为起始原料,以不对称Evans-aldol反应和Julia-Kocienski成烯反应为关键步骤,对大环内酯化合物Iriomoteolide-1b的C(13)-C(23)片段结构进行了合成研究.全文使用普通而廉价的原材料或者试剂,采用常规的容易操作的反应条件,实验成本比较低,并且以13步13%的产率得到了C(13)-C(23)片段结构.     

Synthesis of the C(1)-C(11) polyene fragment of apoptolidin with a new sulfur dioxide-based organic chemistry

A new sulfur dioxide-based organic chemistry has been developed as a novel approach for the stereoselective synthesis of polyene fragments based on our one-pot, four-component synthesis of polyfunctional epsilon-alkanesulfonyl-gamma,delta-unsaturated ketones. The flexibility and efficiency of this methodology are illustrated by the preparation of (+)-methyl (2E,4E,6E,8R,9S)-9-{[(tert-butyl)dimethylsilyl]oxy}-2,4,6,8-tetramethyl-11-(triethylsilyl)undeca-2,4,6-trien-10-ynoate, a synthetic intermediate of Nicolaou and co-workers, that corresponds to the C(1)-C(11) fragment of apoptolidin, which was used by the authors in their total synthesis of this promising anticancer agent.