Stereoselective synthesis of the C1-C10 fragment of rhizoxin D

A novel approach towards the synthesis of the C1-C10 fragment of the biologically active antimitotic agent rhizoxin D is described. The synthesis involves a stereoselective Michael addition reaction of lithium diallyl cuprate with an α,β-unsaturated six membered lactone.     

Synthesis of vinylic iodides for incorporation into the C17-C27 fragment of bryostatins

Vinylic iodides were identified as useful intermediates for the synthesis of the C17-C27 fragment of the bryostatins with control of the geometry of the exocyclic methoxycarbonylmethylene group. Following literature precedent, the Piers (E)-stereoselective addition of tributyltin hydride to an alkynoate followed by ester reduction and tin-iodine exchange gave vinylic iodides that could be used to form the C20-C21 bond of the bryostatins. Chelation controlled addition of lithiated 3-silyloxypropynes to 2-alkoxyaldehydes followed by reductive iodination was used to prepare vinylic iodides that could be used in the complementary assembly of the C21-C22 bond of the bryostatins. Initial studies of the synthesis of intermediates for metathesis studies using metal catalysed reactions of a vinylic iodide for C21-C22 bond formation were complicated by cyclisation reactions.     

Stereoselective synthesis of the C14-C24 degraded fragment of symbiodinolide

Symbiodinolide is a polyol macrolide isolated from the marine dinoflagellate Symbiodinium sp. in 2007. The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, was synthesized stereoselectively from cis-2-butene-1,4-diol. The detailed comparison of the synthetic product with the degraded product in the spectroscopic data confirmed that the stereostructure of the C14-C24 fragment was 17R, 18R, and 21R.     

Studies of the Total Synthesis of Epothilone B and D:A Facile Synthesis of C7-C14 and C15-C21 Fragments

A mild and highly efficient synthesis of C7-C14 and C15-C21 fragments of epothilone B and D is described in which racemic C7-C14 fragment is prepared from nerol through four steps and C15-C21 fragment is obtained from 1,3-dichloroacctone.thioacetamide and propionaldehyde.     

Synthesis of the C1-C9 fragment of callipeltoside-A

[reaction: see text] The C1-C9 fragment of callipeltoside (17) was prepared in 12 steps and 7.2% overall yield from bicyclic lactone (+)-4. Key steps include a stereoselective epoxidation and further regiocontrolled nucleophilic opening of the oxirane ring to install two vicinal stereocenters (C5 and C6), and the use of bis(trimethylsilyl) peroxide and a catalytic amount of Sn(IV) chloride for the chemoselective Baeyer-Villiger oxidation of unsaturated cyclopentanone 15.     

Synthesis of the C21-C34 fragment of antascomicin B

The C21-C34 fragment of the potent FKBP12-binding macrolide antascomicin B was prepared using Ireland-Claisen and allylic diazene rearrangements to establish the C26/C27 and the C23 stereocenters, respectively. Directed hydrogenation installed the C29 β-configuration. The fragment possesses 7 of the 11 fixed stereocenters contained in the natural product.     

Synthesis of C1-C20 and C21-C40 fragments of tetrafibricin

Efficient syntheses of suitably functionalized top and bottom fragments of tetrafibricin are described. The bottom fragment is prepared by two consecutive Kocienski-Julia couplings, while the top fragment synthesis features a dithiane alkylation and a Horner-Wadsworth-Emmons reaction.     

Synthesis of the C8-C20 and C21-C30 segments of pectenotoxin 2

In this study, we synthesized the C8-C20 and C21-C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8-C20 segment was assembled from a phosphonate corresponding to the C8-C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16-C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner-Wadsworth-Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21-C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.     

From furan to open-chain systems. Synthesis of C1-C9 fragment of tylonolide

Stereoselective synthesis of C1-C9 subunit of macrocyclic lactone—tylonolide is presented. Starting from 2-methylfuran and crotyl alcohol, a 2,5-disubstituted furan derivative was synthesized. Its oxidation leads to α,β-unsaturated dicarbonyl intermediate which has been transformed into acyclic fragment bearing five consecutive asymmetric centers.     

Studies on the Synthesis of Reidispongiolide A: Stereoselective Synthesis of the C(22)-C(36) Fragment

A highly stereoselective synthesis of the C(22)-C(36) fragment 2 of reidispongiolide A is described. This synthesis features the highly stereoselective mismatched double asymmetric crotylboration reaction of the aldehyde derived from 5 and the new chiral reagent (S)-(E)-7 that provides 12 with >15:1 dr. Subsequent coupling of the derived vinyl iodide 3 with aldehyde 16 provided allylic alcohol 17, that was elaborated by three steps into the targeted reidispongiolide fragment 2.     

Synthesis of the C12-C24 fragment of peloruside A by silyl-tethered diastereomer-discriminating RCM

The C12-C24 fragment of peloruside A has been synthesized using, as a key step, a silyl-tethered ring closing metathesis reaction to form the C16-C17 (Z)-alkene. The metathesis reaction discriminates between diastereoisomers of the starting material. A diphenylsilyl bis-ether provides simultaneous protection for the C15 and C24 hydroxyl groups, and is expected to lead to high 1,5-anti selectivity in subsequent aldol reactions of the methyl ketone, allowing for a convergent stereoselective synthesis of peloruside A.     

Synthesis and structural determination of the C33-C42 fragment of symbiodinolide

Symbiodinolide (1) is a polyol macrolide with a molecular weight of 2859 mu. As one of the degradation reactions, cross-metathesis of 2, which is a methyl ester of 1, with ethylene was performed to give the C33-C42 degraded fragment 4. The absolute configuration of 4 was estimated to be (36S,40S) by Mosher method. Stereoselective synthesis of 4 was achieved in 14 steps from l-aspartic acid. Synthetic bis-(S)- and (R)-MTPA esters exhibited the spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded fragment 4. Thus, the absolute stereochemistry of 4 was elucidated to be (36S,40S).     

Synthesis of the C21-C28 segment of pectenotoxin-4

The synthesis of the C21-C28 segment of pectenotoxin-4 as the C21 Weinreb amide is described. Feasibility studies for the union of a related Weinreb amide and a functionalized alkyne are also reported.     

Stereoselective synthesis of the C9-C19 lactone-dipropionate fragment of calyculin C

A highly diastereoselective synthesis of the title fragment of calyculin C has been developed based on an internal asymmetric induction between a chiral aldehyde and Z-crotyl trifluorosilane.     

Synthesis of (-)-amphidinolide K fragment C9-C22

[reaction: see text] The key fragment (2a or 2b) in a total synthesis of the cytotoxic macrolide (-)-amphidinolide K (1) has been achieved from synthons C9-C14 (3) and C15-C22 (4), which have both been prepared from glutamic acid in good overall yields.     

Synthesis of macrolide antibiotics Communication 2. Synthesis of the C9-C13 fragment of erythronolides A and C and megalonolide

Conclusions The synthesis of the C⁹-C¹³ fragment of erythromycin A has been accomplished, starting from levoglusan (18 steps, 3.4%).For previous communications, see [1, 2].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2561–2568, November, 1982.     

Synthesis of the C1-C23 fragment of Spirastrellolide A

Synthesis of the C1-C23 fragment in spirastrellolide A is described, featuring a cyclic acetal-tethered RCM for stereoselective constructions of spiroketal, and a 1,3- anti aldol involving methyl ketone enolate and Mukaiyama conditions.     

Synthesis of the C1-C13 fragment of leucascandrolide A

[reaction: see text] The synthesis of the C1-C13 fragment 3 of leucascandrolide A has been completed utilizing a stereoselective and regioselective reductive cleavage of a highly functionalized spiroketal to incorporate the cis-2,6-disubstituted tetrahydropyan. The spiroketal was constructed by addition of a lithiated pyrone 5 to aldehyde 6.     

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.