Complete 1H-NMR spectral assignments for globotriaosyl-Z- and isoglobotriaosyl-E-ceramide

Two-dimensional scalar-correlated (COSY) 1H-NMR spectra of the title compounds, and phase-sensitive COSY spectrum of lactosylceramide, have been fully assigned and some spectral reassignments for related structures suggested. Glycosylation-induced shifts, and shielding by Z- and E-ceramide residues are discussed.     

Total synthesis of solamargine

Solamargine, (25R)-3β-{O-α-l-rhamnopyranosyl-(1→2)-[O-α-l-rhamnopyranosyl-(1→4)]-β-d-glucopyranosyloxy}-22α-N-spirosol-5-ene, has been synthesized in 13 steps in a 10.5% overall yield starting from the naturally abundant diosgenin. Condensation of a partially protected glucopyranosyl donor with an oxaza-spiro moiety, which was formed in one-pot azido reduction, significantly improved the synthesis of desired molecule. The target compound exhibited good cytotoxic activities against tumor cells HeLa, A549, MCF-7, K562, HCT116, U87, and HepG2 with IC₅₀ ranging from 2.1 to 8.0 μM.     

Total synthesis of alpha-galactosyl cerebroside

A highly convergent synthetic approach was developed to obtain alpha-galactosyl cerebroside O-(alpha-D-galactopyranosyl)-2-hexacosylamino-D-ribo-1,3,4-octa decantriol, which has previously been demonstrated to have immunostimulatory activity. Known 4,6-O-benzylidene galactose was the starting material for both the required alpha-galactosyl and the phytosphingosine building blocks O-(2,3-di-O-benzyl-4,6-O-benzylidene-D-galactopyranosyl) trichloroacetimidate (4) and 2-O-methanesulfonyl-D-arabino-1,2,3,4-octadecantetrol (5). The key step of the synthetic strategy is the highly regio- and stereoselective O-galactosylation of 1,3,4-O-unprotected phytosphingosine acceptor 5 using known 4 as donor. The total synthesis required only 11 synthetic steps starting from galactose.     

Total synthesis of gigantetrocin A

A highly efficient synthetic method for the trans-tetrahydrofuran (THF) ring building block was established and the title compound was synthesized in 19 steps from trans-1,4-dichloro-2-butene via a convergent route with a Wittig reaction as the key step.     

Total synthesis and stereochemical reassignment of tasiamide

The total synthesis of a marine acyclic peptide tasiamide and three diastereomers was reported for the first time. The synthesis has led to a reassignment of the N^α‐Me‐L ‐Gln of tasiamide to be N^α‐Me‐D ‐Gln, which was supported by ¹H NMR, ¹³C NMR, COSY, HMQC, HMBC, and optical rotation. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.     

Total synthesis and biological evaluation of methylgerambullone

First total synthesis of methylgerambullone (MGB, 1) isolated from Glycosmis angustifolia was completed via a convergent route. The effect of MGB on the contractile responses of the isolated guinea-pig ileum induced by acetylcholine was investigated. As a result, it showed a potent relaxation rate (78.66 ± 4.30% at 100 mg/L) in a concentration-dependent manner on longitudinal smooth muscle contraction of isolated guinea-pig ileum induced by 1 μM acetylcholine.     

Total synthesis of (+)-crocacin C

Two approaches toward the total synthesis of cytotoxic polyketide natural product (+)-crocacin C (1) are described. The first approach, which was ultimately unsuccessful, was replaced altogether with a second that afforded target 1 in 10 linear steps from commercially available Evans’ chiral propionimide (5% overall yield). No protecting groups were utilized in the total synthesis of 1.     

Total chemical synthesis of enzymes.

The total synthesis, at will, of a wide variety of protein and enzyme molecules is made feasible by modem chemical ligation methods. As Emil Fischer intuitively understood, synthetic access to the enzyme molecule enables the power of chemical science to be applied to elucidating the molecular basis of catalytic function in unprecedented detail.     

Total synthesis and stereochemical reassignment of tasiamide B

The first total synthesis of tasiamide B, an octapeptide bearing 4‐amino‐3‐hydroxy‐5‐phenylpentanoic acid unit isolated from the marine cyanobacteria Symploca sp. is described. A simple and efficient way was found to avoid the pyroglutamylation of N^α‐Me‐Gln and led to a reassignment of the N^α‐Me‐L ‐Phe of tasiamide B to be N^α‐Me‐D ‐Phe, which was also supported by 1D and 2D NMR. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Total synthesis and antifungal evaluation of cyclic aminohexapeptides

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.     

Total synthesis of zervamicin IIB and its deuterium-labelled analogues

For the first time the total synthesis of the peptaibol antibiotic zervamicin IIB is described. Synthesis of this peptaibol was achieved by the Fmoc/tert-butyl strategy in solution using a fragment condensation approach. Three fragments of zervamicin IIB were obtained by stepwise elongation with Fmoc amino acids using BOP as a coupling reagent. For the introduction of the highly sterically hindered α-aminoisobutyric acid residues BOP/DMAP activation was applied. The Fmoc group was removed by reaction with 0.1 M NaOH in dioxane/methanol/water (30/9/1, v/v/v). Peptide fragments were coupled by means of a new coupling reagent, CF₃-PyBOP. Using the strategy developed, zervamicin IIB and two analogues specifically deuterium-labelled at different positions of the glutamine-11 residue have been synthesized in 40% overall yield based on the isotopically labelled amino acid and with 98±2% of isotope enrichment. FAB mass spectroscopy, 600 MHz ¹H-NMR spectroscopy and high-performance liquid chromatography provided convincing evidence that the synthetic products, zervamicin IIB and its deuterium-labelled analogues, fully correspond to the naturally occurring zervamicin IIB. © 1997 European Peptide Society and John Wiley & Sons, Ltd.     

Total synthesis and biological evaluation of spirotryprostatin A analogs

Based on the spirotryprostatin A structure, a series of compounds belonging to spiro‐indolyl diketopiperazine structural class were designed and synthesized, which embody an oxindole with an all‐carbon quaternary stereocenter. The total synthesis can efficiently be accessed in a seven‐step reaction sequence with 18–28% overall yield from commercially available materials, and a highly enantioselective 1,3‐dipolar cycloaddition, N ‐acylation of the resulting stereochemically complex spiro[pyrrolidin‐3,3′‐oxindole]s core with Fmoc‐L ‐pro‐Cl and spontaneous ring closure upon N ‐deprotection were obtained. The synthesized compounds 13a–e and 15a–e were evaluated for their antibacterial activities. The result showed that compounds 13b and 15b were active only against Gram‐positive bacteria, and selective antibacterial activity was exhibited by compounds 13d and 13e against Streptococcus lactis . Further, all the remaining compounds showed a certain degree of antibacterial activity. In addition, the structure–activity relationship is also discussed.     

Total synthesis of diazasteroids (1).

Contrary to previous reports, the condensation product of 8-aminoquinoline (1) and 2-carbethoxycyclopentanone (2) undergoes ring closure with polyphosphoric acid to give the 1, 11-diazasteroid 5. Catalytic hydrogenation reduced the A ring and the double bond to produce 6. 8-Aminotetrahydroquinoline (7) and 3-carbethoxy-2-piperidone condense to a tricyclic intermediate (11), which could not be cyclized to a steroid, however.     

Total synthesis of sialosylcerebroside, GM4

Described are total syntheses of O-[sodium (5-acetamido-3,5-dideoxy-D -glycero-alpha-D-galacto-2-nonulopyranosyl)onate]-(2----3)-O -beta-D -galactopyranosyl-(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingen ine,O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl+ ++)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine, O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-beta-D-gal act opyranosyl -(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingenine, and O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl++ +)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine by using O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D -galacto-2-nonulopyranosyl)onate]-(2----3)-2,3,4,6-tetra-O-a cetyl-D -galactopyrano-syl trichloroacetimidate and O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-2,4,6-tri-O-ace tyl-D-galactopyranosyl trichloroacetimidate as key glycosyl donors, and (2S,3R,4E)-3 -O-benzoyl-2-N-tetracosanoylsphingenine as a key glycosyl acceptor.     

Total enzymatic synthesis of cholecystokinin CCK-5

Summary. This paper describes the enzymatic synthesis of the C-terminal fragment H-Gly-Trp-Met-Asp-Phe-NH₂ of cholecystokinin. Immobilized enzymes were used for the formation of all peptide bonds except thermolysin. Beginning the synthesis with phenylacetyl (PhAc) glycine carboxamidomethyl ester (OCam) and H-Trp-OMe by using immobilized papain as biocatalyst in buffered ethyl acetate, the dipeptide methyl ester was then coupled directly with Met-OEt·HCl by -chymotrypsin/Celite 545 in a solvent free system. For the 3+2 coupling PhAc-Gly-Trp-Met-OEt had to be converted into its OCam ester.The other fragment H-Asp(OMe)-Phe-NH₂ resulted from the coupling of Cbo-Asp(OMe)-OH with H-Phe-NH₂·HCl and thermolysin as catalyst, followed by catalytic hydrogenation.Finally PhAc-Gly-Trp-Met-Asp-Phe-NH₂ was obtained in a smooth reaction from PhAc-Gly-Trp-Met-OCam and H-Asp(OMe)-Phe-NH₂ with -chymotrypsin/Celite 545 in acetonitrile, followed by basic hydrolysis of the -methyl ester. The PhAc-group is removed with penicillin G amidase and CCK-5 is obtained in an overall isolated yield of 19.6%.     

Total synthesis of human plasma apolipoprotein C-II

Apolipoprotein C-II (apoC-II), a protein of 79 amino acid residues present in very low density lipoproteins, enhances the lipoprotein lipase (LpL)-catalyzed hydrolysis of triacylglycerols transported in plasma triglyceride-rich lipoproteins. To elucidate the structure-activity relationship of this activator protein, the complete amino acid sequence of apoC-II has been synthesized by the solid-phase method with Boc-amino acid derivatives and phenylacetamidomethyl resin. The crude peptide was purified to homogeneity in 10% yield by a combination of ion-exchange and preparative high-performance liquid chromatography (HPLC). The purified peptide had the expected amino-terminal sequence and amino acid composition. Synthetic and native apoC-II were indistinguishable by cochromatography on analytical HPLC, peptide mapping of tryptic digest, radioimmunoassay, and activation of LpL with both artificial and lipoprotein substrates.