Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of a fully elaborated GHIJ-ring fragment

A stereocontrolled synthesis of a fully elaborated GHIJ-ring fragment of gambieric acids, which are potent antifungal polycyclic ether natural products, has been accomplished. The synthesis features convergent assembly of the tetracyclic polyether skeleton through aldol coupling/cyclodehydration/reductive etherification processes and stereoselective construction of the J-ring side chain by a CeCl₃-promoted Julia-Kocienski olefination.     

A convergent stereocontrolled total synthesis of (-)-terpestacin

A stereocontrolled total synthesis of (-)-terpestacin has been achieved starting from (R)-(-)-carvone as a chiral pool and (E,E)-farnesol via a highly convergent approach. Thus, (R)-(-)-carvone was transformed into the cyclopentanone segment through a series of high yielding operations with the proper setup of all the stereochemical centers while (E,E)-farnesol was converted into the other requisite building block via a series of high yielding reactions. The cyclopentanone intermediate was both selectively enolized and alkylated at room temperature to yield the desired coupling product, which provided the natural product upon further transformations.     

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.     

Toward fully synthetic glycoproteins by ultimately convergent routes: a solution to a long-standing problem

A method is disclosed for the convergent synthesis of multiply glycosylated peptides. The approach centers on a convergent technique for generating masked, complex glycopeptide-containing C-terminal acyl donors. Activation of the latent donor in situ and use directly in segment coupling with a second peptide bearing a complex carbohydrate produces a completely unprotected, bifunctional glycopeptide. The system demonstrates a minimum level of hydrolysis and epimerization at the C-terminal amino acid residue of the acyl donor during fully convergent segment coupling and is therefore a powerful tool for the synthesis of glycoproteins.     

Efficient and convergent stereocontrolled spiroannulation of ketones

Upon treatment with tBuOK/H₂O, a variety of ω-halo-β-keto-ketals undergo smooth cyclisation, affording in excellent yields mono-protected [n,m] spiro bicyclic diketones. This transformation is highly stereoselective producing, in all cases, the diastereoisomerically pure spiro derivatives.     

A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway

A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C(20) to C(35) in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction.     

Rapid stereocontrolled assembly of the fully substituted C-aryl glycoside of kendomycin with a Prins cyclization: a formal synthesis

Prins cyclization using an electron-rich benzaldehyde and a homoallylic alcohol efficiently delivered the fully substituted C-aryl tetrahydropyranoside of kendomycin.     

Enantioselective synthesis of an aziridinomitosane and selective functionalizations of a key intermediate

An enantioselective synthesis of mitosane core (-)-1 has been achieved. Key steps include a rapid assembly of a key eight-membered-ring intermediate employing ring-closing metathesis. Kinetic resolution of an advanced secondary alcohol was then accomplished by using a peptide-based asymmetric acyl transfer catalyst that was discovered from a parallel screen of catalyst candidates. Optically pure material was then converted to the mitosane core, which was the subject of additional studies on the selective modification to produce several substituted compounds containing a mitosane ring system.     

Nanomaterials of triazine-based dendrons: convergent synthesis and their physical studies

[structure: see text] Without employing protection and deprotection processes, two series of triazine-based dendrons were efficiently prepared by a convergent method and fully characterized; their physical properties, including acidic, thermal, electrical, and optical stabilities were also studied.     

Chemical synthesis of cellulose derivatives by a convergent synthetic method and several of their properties

Two homologous series of regio- selectively sub stituted cellulose: 3-O-benzyl-2, 6-di-O-pivaloyl derivatives (Series 1) and 2,3,6-tri-O-acetyl derivatives (Series 2) up to an eicosamer (DP = 20), were synthesized for the first time by elongation of the carbohydrate chain from cellooctaose derivative 5 and subsequent deprotection. Some changing properties of the homologous series with increasing DP were examined. Gel permeation chromatography (GPC) analysis for series 1 and 2 indicated that plots of log M vs retention time gave a straight line. The plots of [M]n/n vs (n – 1)/n (where [M]n is the molecular rotation for an oligomer with DP = n) up to a hexadecamer 9 in series 2 gave straight lines, although the result for the eicosamer 11 deviated somewhat from the line     

Synthetic studies toward GKK1032s, novel antibiotic antitumor agents: enantioselective synthesis of the fully elaborated tricyclic core via an intramolecular Diels-Alder cycloaddition

An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels-Alder reaction between a siloxydiene and an optically active enone derived from D-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.     

New synthetic strategies for the stereocontrolled synthesis of substituted ‘skipped’ diepoxides

This report describes a number of new synthetic approaches toward methyl-substituted mono- and diepoxy alcohols that serve as substrates for endo-selective epoxide-opening cascades. The key transformations involve the manipulation of alkynes. Highlighted are the directed methylmetalation of bishomopropargylic alcohols, the bromoallylation of alkynes, and Pd-catalyzed cross-coupling between an alkenyl boronate ester and allylic bromides.     

(+)-Phorboxazole A synthetic studies. A highly convergent, second generation total synthesis of (+)-phorboxazole A

[structure: see text] A second generation total synthesis of the potent antitumor agent (+)-phorboxazole A (1) has been achieved. The cornerstone of this approach comprises a more convergent strategy, involving late-stage Stille union of a fully elaborated C(1-28) macrocycle with a C(29-46) side chain. The second generation synthesis entails the longest linear sequence of 24 steps, with an overall yield of 4.2%.     

Electro-inorganic synthesis: a convergent paired electrochemical synthesis and voltammetric studies of copper(II)-2-aminophenol derivatives

Electrochemical reduction of 2-nitrophenol and 5-methyl-2-nitrophenol has been studied in water/ethanol mixture using cyclic voltammetry and controlled-potential coulometry. Our voltammetric data indicate the formation of 2-aminophenol (HL^I) and 5-methyl-2-aminophenol (HL^II), respectively. Also, the electrochemical synthesis of copper(II) complex of 2-aminophenols has been carried out using copper metal as a sacrificial anode and lead metal as a cathode in water/ethanol (50/50 v/v). The electrochemical synthesis of copper(II)-2-aminophenols consists of a multi-step such as (a) cathodic reduction of 2-nitrophenols to related 2-aminophenols, (b) generation of Cu²⁺ from copper anode, (c) complexation of 2-aminophenols with Cu²⁺. In this work, we have proposed a mechanism for the electrode process. Some parameters such as electrode material, current density, electricity passed and temperature, were also systematically studied. The convergent paired electrochemical synthesis of copper(II) complex of 2-aminophenols has been successfully performed in a one-pot process, under constant current condition in an undivided cell, in a good yield and purity. Also, the electrochemical behavior of copper(II)-2-aminophenol complex was studied and the stability constant of copper(I)-2-aminophenol complex was evaluated using cyclic voltammetry.     

Formal total synthesis of altohyrtin C (spongistatin 2). Part 2: Construction of fully elaborated ABCD and EF fragments

Coupling of the C1C14 (AB) crotylstannane with the C15C28 (CD) aldehyde followed by stereochemical arrangements gave the C1C28 (ABCD) fragment of altohyrtin C. The C29C44 (EF) fragment was also prepared. The syntheses of these two fragments, both of which were identical with those prepared by the Smith group, constitute a formal total synthesis of altohyrtin C.     

Late-stage lipidation of fully elaborated tryptophan-containing peptides for improved pharmacokinetics

The late-stage modification of native peptides to alter and/or enhance their properties and functions is attractive but formidably challenging. Peptide lipidation is one of the effective strategies to overcome short half-life and rapid clearance. Herein, we report a late-stage installation of a fatty acid lipid onto fully elaborated peptides, using glucagon as an example, through regio- and chemoselective functionalization of tryptophan with high potency and remarkable in vivo half-life extension.     

Synthetic studies of the HIV-1 protease inhibitive didemnaketals: stereocontrolled synthetic approach to the key mother spiroketals

The stereocontrolled synthesis of (2S,4R,6R,8S,10S,1'R,1' 'R)-2(acetylhydroxymethyl)-4,10-dimethyl-8(isopropenylhydroxymethyl)-1,7-dioxaspiro[5,5]undecane (4a) and its C1' '-epimer (4b), the key mother spiroketals of the HIV-1 protease inhibitive didemnaketals from the ascidian Didemnum sp., has been carried out through multisteps from the natural (R)-(+)-pulegone, which involved the diastereoselective construction of four chiral carbon centers(C-2, C-6, C-8, and C-1') by intramolecular chiral induce.     

Efficient stereocontrolled synthesis of sitagliptin phosphate

The synthesis of sitagliptin phosphate 1, a novel DPP-IV inhibitor for the treatment of type 2 diabetes mellitus has been accomplished starting from the chiral synthon (1,4-bis[(R)-1-phenylethyl]piperazine-2,5-dione) 2, involving highly stereocontrolled (>98%) alkylation as a key step, in a good overall yield of 50% over six steps.     

A stereocontrolled synthesis of delta-trans-tocotrienoloic acid

[reaction: see text] A concise stereoselective total synthesis of a naturally occurring polymerase beta inhibitor, delta-trans-tocotrienoloic acid (2), is described. The key step in the synthesis is an acid-catalyzed cyclodehydration reaction. Additionally, this report corrects a previously reported structural assignment, defines the absolute stereochemistry of 2, and defines key structural requirements for polymerase beta inhibition.