Total synthesis of five proline-enriched cyclic heptapeptides from the marine sponge Stylissa carteri

The total synthesis of five naturally occurring cyclic proline-enriched heptapeptides from the marine sponge Stylissa carteri was reported. The five cyclic heptapeptides were synthesized by applying a two-step solid-phase/solution synthesis strategy. The linear heptapeptides were assembled by standard Fmoc chemistry on 2-chlorotrityl chloride resin, cleaved off-resin with acetic acid/trifluoroethanol/dichloromethane to keep side-chain protecting groups intact, and subsequently cyclization was achieved by a solution method. The final products were purified by a preparative RP-HPLC system, and their structures were characterized by HR-QTOF-MS NMR. The spectral data of synthetic peptides were found to be identical to that reported for the natural products.     

Synthesis of the cyclic heptapeptide axinellin A

The first synthesis of the naturally occurring cyclic peptide axinellin A has been achieved. Cyclization and subsequent deprotection of linear precursors containing either a t-butyl protected Thr residue or a Thr(Ψ^Me,Mepro) derivative gave a cyclic peptide, identical in all respects to the naturally occurring material, with the exception that the synthetic peptide does not exhibit the cytotoxic activity reported for the natural product.     

Solid-phase synthesis of homodetic cyclic peptides from Fmoc-MeDbz-resin

Cyclic homodetic peptides are very appealing for medicinal chemistry programs. In addition to the high efficiency and selectivity inherently associated with peptides, a cyclic structure totally formed by amide bonds increases their stability under physiological conditions. Here Fmoc-MeDbz-resin was studied for the preparation of these peptides. Our results demonstrate the usefulness of this strategy for the preparation of cyclic “head-to-side chain” peptides through cyclative cleavage (simultaneous cyclization and release from the resin). In contrast, for the synthesis of the “head-to-tail” counterparts, the cyclization-cleavage should be carried out in the presence of thiophenol.     

Traceless solid-phase synthesis of multiple sulfonamide-containing cyclic sulfides exploiting microwave irradiation

In this Letter, a new synthetic method of sulfonamide-containing cyclic sulfides using a microwave-assisted traceless solid-phase approach is described. Using this new method, many highly pure cyclic sulfides were efficiently synthesized based on intramolecular alkylation of the sulfides followed by elimination of the desired products from the generated sulfonium salts.     

Synthesis of a highly hydrophobic cyclic decapeptide by solid-phase synthesis of linear peptide and cyclization in solution

<正>A general method was described to synthesize a highly hydrophobic cyclic peptide,cyclo[LWLWLWLWLQ]where underlines indicate D-configuration of the amino acid,by a two-step solid-phase/solution synthesis strategy.The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC,50%(v/v) DMF/H_2O was employed as the solvent to overcome the difficulty of solubilization for the hydrophobic cyclic decapeptide and achieved a total yield of 30-35%with a purity of over 98%.     

Total synthesis and modification of proline-rich cyclopeptides Phakellistatins 17 and 18 isolated from marine sponge

The Phakellistatins 17 and 18, two naturally occurring cyclic proline-rich peptides from marine sponge, were synthesized by utilizing a two-step solid-phase/solution synthesis strategy for the first time. Phakellistatin 18 exhibited a weak inhibitory activity against human lung carcinoma cell (A549) and human hepatoma (BEL-7042). In order to improve the activity of Phakellistatin 18, two of its analogues which contain sulfonyl fluoride group (P18-1) and arginine substituted derivative (P18-2) were also synthesized respectively. The spectral data of Phakellistatins 17 and 18 were identical to that reported for the natural products. Analogues P18-1 and P18-2 were identified by means of HR-QTOF-MS, ¹H NMR and ¹³C NMR. More importantly, analogue P18-1 exhibited significantly enhanced cytotoxicity against BEL-7042 cancer cells compared with Phakellistatin 18, suggesting that the sulfonyl fluoride group in the parent peptide may contribute to the improvement of antitumor activity. This strategy provides a reference method for improving the activity of natural peptides. reserved.     

Solid-phase synthesis of cyclic hexapeptides wollamides A,B and desotamide B

Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cocktail of trifluoroacetic acid/triisopropylsilane/dichloromethane afforded the desired cyclic hexapeptides, which were characterized by ¹H, ¹³C NMR, and HRMS. Subsequent investigation of macrocyclization parameters such as terminal residues, coupling reagents, and cyclization concentration revealed the optimized conditions for the synthesis of this class of cyclic hexapeptides.     

A solid-phase total synthesis of the cyclic depsipeptide HDAC inhibitor spiruchostatin A

Spiruchostatin A, a potent histone deacetylase inhibitor, was efficiently synthesized from (3S,4R)-4-amino-3-hydroxy-5-methylhexanoic acid utilizing solid-phase peptide elongation with d-cysteine, d-alanine, and (E)-3-hydroxy-7-thio-4-heptenoic acid and solution-phase macrolactonization, followed by intramolecular disulfide formation.     

Acyclic and cyclic thioenamino peptides: solution- and solid-phase synthesis

Seven- and 10-membered cyclic thioenamino peptides, that is, 1,4-thiazepinone (11) and cyclic thioenamino peptide 9 (which represents a potential γ-turn mimetic), were synthesized, and the structure of 11 was secured by X-ray diffraction analysis of its TFA salt. The aforementioned compounds were prepared in solution and by solid-phase synthesis. Additionally, we have prepared thioenamino diketopiperazine synthon 16.     

(−)-Ternatin, a highly N-methylated cyclic heptapeptide that inhibits fat accumulation: structure and synthesis

A highly N-methylated cyclic heptapeptide, (−)-ternatin, was isolated from the mushroom Coriolus versicolor, which significantly suppressed fat accumulation against 3T3-L1 murine adipocytes (EC₅₀ = 0.14 μg/mL). Although ternatin was previously reported to be antibacterial or antimicrobial compound, its inhibitory effect on fat accumulation has been first shown. The structure of (−)-ternatin was revised to be a cyclo [d-allo-Ile¹-l-(NMe)Ala²-l-(NMe)Leu³-l-Leu⁴-l-(NMe)Ala⁵-d-(NMe)Ala⁶-(2R,3R)-3-hydroxy-Leu⁷] by spectroscopic analysis and chemical synthesis.     

Synthesis of cyclic peptide reniochalistatin E and conformational isomers

Here we describe a convergent synthesis of reniochalistatin E that utilized solid-phase peptide synthesis. For macrolactamization of the linear peptides without the side chain protecting group, we obtained reniochalistatin E and its conformational isomers with 32% isolation yield.     

A simple and efficient synthesis of new cyclic ureas

A facile access to a wide range of original saturated N-heterocyclic ureas is described using, as a key step, a Michael-type reaction involving isocyanates or amines on a piperidine framework possessing an α,β-unsaturated ester functionality.     

Total synthesis of phorboxazole B

An efficient and highly convergent total synthesis of the potent antitumor agent phorboxazole B has been achieved. The synthetic strategy of this synthesis features: 1) a highly efficient substrate-controlled hydrogenation to construct the functionalized cis-tetrahydropyrane unit; 2) iterative crotyl addition to synthesize the segment that contains alternating hydroxyl and methyl substituents; 3) Hg(OAc)2/I2-induced cyclization to establish the cis-tetrahydropyrane moiety; 4) 1,3-asymmetric induction in the Mukaiyama aldol reaction to afford the stereogenic centers at C9 and C3; and 5) the exploration of the Still-Gennari olefination reaction to complete the macrolide ring of phorboxazoloe B.     

Total synthesis of dapiramicin B

The first total synthesis of dapiramicin B, a nucleoside antibiotic, is described. The characteristic N-glycoside linkage in dapiramicin B was effectively constructed by way of the Pd-catalyzed coupling reaction of a heptopyranosylamine with a bromopyrrolopyrimidine derivative.     

Facile solid-phase synthesis of head-side chain cyclothiodepsipeptides through a cyclative cleavage from MeDbz-resin

Head to side-chain cyclothiodepsipeptides were conveniently prepared through a cyclative cleavage using the MeDbz linker. Briefly, the peptide sequence was elongated on a MeDbz-Gly-ChemMatrix resin and reacted with 4-nitrophenyl chloroformate, followed by treatment with DIEA to render an activated cyclic N-acyl-N′-methylurea-resin. Removal of the Cys protecting group and further treatment with DIEA allowed the formation of the thiolactone with the concomitant release of the cyclic peptide from the resin.     

Total synthesis of rac-longamide B

rac-Longamide B has been synthesized in six-steps from known starting materials. The synthesis is highlighted by a novel palladium-catalyzed double allylic alkylation of amidopyrroles with 2-butene-1,4-di-tert-butyl dicarbonate.     

Total synthesis of emericellamides A and B

The total synthesis of emericellamides A and B is reported. A convergent, flexible strategy employing peptide chemistry, asymmetric alkylations, and culminating in macrolactamization is described. The previously reported structure of both compounds is confirmed.     

Total synthesis of (−)-radicamine B

The synthesis of a chiral cyclic nitrone with l-arabino configuration and its application in the total synthesis of radicamine B is reported. An agreement in the spectral data with natural radicamine B but specific rotation with an opposite sign warranted a revision of the absolute configuration of radicamine B.     

Total synthesis of Yingzhaosu B and its three diastereoisomers

Yingzhaosu B (1), coexisting with Yingzhaosu A (2) which is an antimalarialprinciple in the traditional Chinese herbal medicine Yingzhao (Artabotrys uncina-tus (L.) Merr.), is a polyhydroxy bisabolene compound. Although its structure wasproposed by Liang and coworkers in 1979, the stereochemistry remained unsettled.From biogenetic viewpoint, it is reasonable to assume that the configuration of 4-Cin Yingzhaosu B is S as that in Yingzhaosu A. Recently, the synthesis of degrada     

Total synthesis of the tricyclic humulanolide wilfolide B

The first total synthesis of tricyclic humulanolide wilfolide B was achieved. The synthetic strategy involved: i) radical cyclization with samarium(II) iodide to construct the bicyclic lactone from an acyclic compound, and ii) ring-closing metathesis to build the eight-membered ring by connecting two side chains, thus completing the tricyclic framework.