Synthetic studies toward amphidinolide B1: synthesis of the C9-C26 fragment

[reaction: see text] The synthesis of the C9-C26 portion of amphidinolide B1 is described. A Fleming allylation followed by elimination was employed for the construction of the C13-C15 diene portion. Sharpless asymmetric dihydroxylation was utilized for regioselective functionalization of a styrene-derived alkene, in the presence of the C13-C15 diene functionality. A highly diastereoselective aldol reaction was developed to establish the C18 stereochemistry.     

Stereoselective synthesis of C1-C9 and C9-C17 fragments of (+)-13-deoxytedanolide

An efficient and highly stereoselective asymmetric synthesis of C1-C9 and C9-C17 fragments of (+)-13-deoxytedanolide have been achieved. Utilization of desymmetrization technique to prepare the triol with five stereogenic centers, regioselective Sharpless asymmetric dihydroxylation, Evans' aldol reaction, chiral methylation, and Wittig olefination are highlights of the synthesis.     

Spirastrellolide B: the synthesis of southern (C9-C25) region

A combination of "chiron" and "asymmetric" approaches is utilized to construct the southern (C 9-C 25) region of marine natural product spirastrellolide B. The key functionalities are derived from d-glucose and Sharpless asymmetric epoxidation and dihydroxylation.     

Stereoselective synthesis of the densely functionalized C1-C9 fragment of amphidinolides C and F

The synthesis of the C1-C9 subunit of amphidinolides C and F is described. Key steps include tandem Sharpless asymmetric dihydroxylation-S_N2 cyclization reaction, Lewis acid-mediated epoxide opening, Wittig reaction, and Wacker oxidation.     

Total synthesis of scytophycin C. 1. Stereoselective syntheses of the C(1)-C(18) segment and the C(19)-C(31) segment

[structure: see text] Stereoselective total synthesis of scytophycin C, a marine 22-membered macrolide displaying potent activity against a variety of human carcinoma cell lines, has been reported in which the polypropionate structure bearing contiguous asymmetric centers was stereospecifically constructed by using new acyclic stereocontrol. This paper describes stereoselective syntheses of the C(1)-C(18) segment (Segment A) including a trans-disubstituted dihydropyran ring and the C(19)-C(31) segment (Segment B) having eight stereogenic centers.     

Studies towards the total synthesis of cruentaren A and B: Stereoselective synthesis of fragments C1-C11, C12-C22 and C23-C28

A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn-stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti-stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis-2-butene-1,4-diol respectively.     

Synthesis of the C1-C16 fragment of spirastrellolide A

Synthesis of the C1-C16 fragment of spirastrellolide A is described here featuring Sharpless asymmetric epoxidation, an acid promoted O-1,4-addition, and Mukaiyama 1,3-anti-aldol.     

Synthetic studies toward the C5-C20 domain of the azaspiracids

[structure: see text]. An approach toward the C5-C20 THF-fused trioxadispiroketal portion of the azaspiracids is reported. The highly substituted azaspiracid D ring (C16-C19) was prepared by the one-pot conversion of a tetraol into a tetrahydrofuran. Efforts to establish the C10 and C13 spiroketal centers via an oxonium-initiated bis-spiroketalization under both kinetic and thermodynamic conditions have yielded the (10R,13S)-trioxadispiroketal 19 as the major product, which is diastereomeric with the (10R,13R) relative configuration assigned to the azaspiracids.     

Synthetic studies of the 18-membered antitumor macrolide, tedanolide. 3. Stereocontrolled synthesis of the C1-C12 part via a synthesis of the C1-C7 fragment by a mismatched but efficient sharpless dihydroxylation and its coupling with the C8-C11 fragment

The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).     

Formal total synthesis of borrelidin: synthesis of C1-C11 fragment via desymmetrization strategy

A stereoselective formal total synthesis of borrelidin is described. The synthetic strategy for synthesis of C1-C11 fragment features desymmetrization of Diels-Alder adduct, Sharpless asymmetric epoxidation, regioselective opening of chiral epoxide, and alkylation using Evans chiral auxiliary.     

A second-generation synthesis of the C1-C28 portion of the altohyrtins (spongistatins)

A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.     

Stereoselective synthesis of the C33-C44 fragment of palau’amide

An efficient stereoselective synthesis of the C33-C44 fragment of palau’amide is described using a Sharpless asymmetric epoxidation, a regioselective nucleophilic ring opening of the epoxide, a Grignard reaction and a Luche stereoselective reduction of a keto compound as the key steps.     

Toward the second generation synthesis of aplyronine A: stereocontrolled assembly of the C1-C19 segment by using an asymmetric Nozaki-Hiyama-Kishi coupling

An efficient synthesis of the C1-C19 segment of aplyronine A is described. Stereoselective construction of the C14-C15 (E)-trisubstituted double bond and the C13 stereocenter was achieved by using an asymmetric Nozaki-Hiyama-Kishi coupling.     

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.     

Trifluoromethyl derivatives of insoluble small-HOMO-LUMO-gap hollow higher fullerenes. NMR and DFT structure elucidation of C2-(C74-D3h)(CF3)12, Cs-(C76-Td(2))(CF3)12, C2-(C78-D3h(5))(CF3)12, Cs-(C80-C2v(5))(CF3)12, and C2-(C82-C2(5))(CF3)12

Reaction of a mixture of insoluble higher fullerenes with CF3I at 500 degrees C produced a single abundant isomer of C74(CF3)12, C76(CF3)12, and C80(CF3)12, two abundant isomers of C78(CF3)12 and C82(CF3)12, and an indeterminant number of isomers of C84(CF3)12. Using a combination of 19F NMR spectroscopy, DFT calculations, and the structures and spectra of previously reported fullerene(CF3)n compounds, the most-probable structures of six of the seven isolated compounds were determined to be specific isomers of C2-(C74-D3h)(CF3)12, Cs-(C76-Td(2))(CF3)12), C2-(C78-D3h(5))(CF3)12), Cs-(C80-C2v(5))(CF3)12), C2-(C82-C2(5))(CF3)12), and C2-(C82-C2(3))(CF3)12) containing ribbons and/or loops of edge-sharing para-C6(CF3)2 hexagons. The seventh isolated compound is a C1 isomer of C78(CF3)12 containing two such ribbons. This set of compounds represents only the second reported isolable compound with the hollow C74-D3h cage and the first experimental evidence for the existence of the hollow fullerenes C76-Td(2), C78-D3h(5), C80-C2v(5), and C82-C2(5) in arc-discharge soots.     

Toward the synthesis of spirastrellolide a: construction of a tetracyclic C26-C40 subunit containing the DEF-bis-spiroacetal

[reaction: see text] A stereo-controlled synthesis of the fully elaborated C26-C40 tricyclic [5,6,6]-bis-spiroacetal of spirastrellolide A containing the C28 chlorine substituent is reported, exploiting asymmetric Sharpless dihydroxylation and boron-mediated allylation methodology.     

Halichondrin B: synthesis of the C(1)-C(15) subunit

A short and efficient synthesis of the C(1)-C(15) subunit of halichondrin B in its natural configuration is described. The polycyclic caged ketal 3, containing nine asymmetric centers, is prepared in 14 steps from alpha-D-glucoheptonic acid gamma-lactone (7). Key steps in the two similar routes described include EtMgBr-promoted pinacol ring expansions of hydroxy mesylates 23 and 34, intramolecular Michael additions of 29 and 37, and a one-pot, HF-induced conversion of 4 to 3involving in situ silyl ether cleavage, acetal hydrolysis, Michael addition, and caged ketal formation. Alternative protocols for carbinol inversion at C(11), one early and one late in the synthetic sequence, are also described.     

Synthetic studies on antascomicin A: construction of the C18-C34 fragment

Stereoselective synthesis of the C18-C34 fragment of antascomicin A is described. Construction of the C27-C34 carbocycle moiety was achieved via catalytic Ferrier carbocylization and Johnson-Claisen rearrangement, which was converted to iodide 2 by use of asymmetric alkylation and Sharpless epoxidation as key transformations. Coupling of iodide 2 and sulfone 3 furnished the C18-C34 fragment.     

Studies on the synthesis of apoptolidin: synthesis of a C1-C27 fragment of apoptolidin D

Synthesis of a C(1)-C(27) fragment, a key intermediate in the synthesis of apoptolidin D, is reported. The synthesis involves a combination of Heck coupling and Horner-Wadsworth-Emmons reaction for the C(1)-C(7) trienoate portion and an efficient Suzuki cross-coupling protocol for the C(10)-C(13) diene portion.     

Synthesis of amphidinolide E C10-C26 fragment

The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an oxolane-containing C10-C17 segment (9, derived from L-glutamic acid) via a Julia-Kocienski reaction with aldehyde 3, followed by a Sharpless AD to obtain the desired diol. The C22-C26 fragment was installed by means of an efficient Suzuki-Molander coupling, with an organotrifluoroborate reagent (4, arising from a cross-metathesis reaction between a vinylboronate and 2-methyl-1,4-pentadiene).