Two New Indolyl Diketopiperazines,Trypostatins C and D from Aspergillus penicilliodes Speg.

Twelve indolyl diketopiperazines 1-12 were isolated from the mycelia culture of Aspergillus penicilliodes Speg.,a dominant microorganism from the post fermentation process of ripe Pu-er tea.Their structures were elucidated by extensive spectroscopic methods.Among them,trypostatins C(1)and D(2)featuring with a rare methyl vinyl ketone side chain at C-2 are new compounds,while 3 and 4 were obtained for the first time from nature source.The isolates 3-12 did not show obvious cytotoxicities against five human cancer cell lines at a concentration of 40μM.

Antibacterial sorbicillin and diketopiperazines from the endogenous fungus Penicillium sp. GD6 associated Chinese mangrove Bruguiera gymnorrhiza

One new sorbicillin derivative, 2-deoxy-sohirnone C(1), one new diketopiperazine alkaloid, 5 S-hydroxynorvalineS-Ile(2), and two naturally occurring diketopiperazines, 3 S-hydroxylcyclo(S-Pro-S-Phe)(3) and cyclo(S-Phe-S-Gln)(4), together with three known compounds were isolated from the Chinese mangrove endophytic fungus Penicillium sp. GD6. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison with literature data. The absolute configuration of 3-hydroxyl moiety in 3 was determined by Mosher's method, while the absolute stereochemistry of 2 and 4 was established by comparison with the CD spectra of natural and synthesized diketopiperazines. Compound 1 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with a MIC value of 80 μg·m L^(-1).

Secondary Metabolites of a Deep Sea Derived Fungus Aspergillus versicolor CXCTD-06-6a and Their Bioactivity

In order to obtain novel secondary metabolites, a deep sea inhabiting fungus Aspergillus versicolor CXCTD-06-6a was investigated. One new diketopiperazine brevianamide W(1a), as well as five known diketopiperazine alkaloids, diketopiperazine V(1b), brevianamide Q(2), brevianamide R(3), brevianamide K(4), and brevianamide E(5), were isolated from the Et OAc extract of the fermentation broth. Their structures were elucidated by spectroscopy techniques(NMR, MS). The six compounds exhibited moderate radical scavenging activity against DPPH with clearance ratio of 55.0%(1a and 1b), 53.7%(2), 46.2%(3), 61.4%(4) and 19.3%(5) at a concentration of 13.9 μmol L-1, respectively; while the positive control ascorbic acid showed a ratio of 70.3% at the concentration of 28.4 μmol L-1.

Synthesis and Pharmacokinetic Property Improvement of Deuterated Plinabulin 9

Plinabulin,a potent microtubule-targeting agent,is derived from marine natural diketopiperazine ‘phenylahistin'.To develop novel plinabulin analogue that could display better pharmacokinetic properties and less side effects,deuterated plinabulin 9 was synthesized and evaluated in vitro and in vivo.In comparison with plinabulin,in vivo pharmacokinetic studies indicated that the deuterated derivative 9 could alter blood circulation behavior obviously,which was proved by increased area under the plasma concentration-time curve(AUC_(0–∞)),reduced clearance(CL),and prolonged total body mean residence time(MRT).The derivative 9 also has higher inhibition rates against Bx PC-3,Jurkat and A-431 tumor cell lines as compared with its prototype plinabulin.Therefore,the deuterated compound 9 might be developed as a potential agent for different cancer treatments.

A New Route for the Synthesis of N-Substituted Diketopiperazine Derivatives

Eight N-substituted diketopiperazines （DKPs） were synthesized by solid-phase protocols. The introduction of iminodiacetic acid （Ida） and followed another a-amino acid residue as the precursor of DKP framework made the present synthesis to be very facile and efficient.

A cytotoxic pyrrolidinoindoline diketopiperazine dimer from the algal fungus Eurotium herbariorum HT-2

A new cytotoxic pyrrolidinoindoline diketopiperazine dimer, cristatumin E （1）, was isolated from the fermentation broth of the algal fungus Eurotium herbariorum HT-2 associated with the marine algae, Enteromorpha prolifera. The structure was determined by spectroscopic analyses and Marfey＇s amino acid analysis. Cristatumin E （1） showed cytotoxicity against K562 tumor cell line and antibacterial activity against Enterobacter aerogenes and Escherichia coli with IC50 and MIC values of 8.3, 44.0 and 44.0 μmol/L, respectively.

Dysamide U,a new trichlorinated diketopiperazine from the sponge Dysidea sp.

Dysamide U, a new trichlorinated diketopiperazine (1) along with seven known ones (2–8) were isolated from the sponge of Dysidea sp. collected from the Pacific ocean. The structure of dysamide U (l) was elucidated by high resolution FABMS and 1H NMR data including COSY and RCT-COSY.

Three nitrogen-containing metabolites from an algicolous isolate of Trichoderma asperellum

As one of the most productive species,Trichoderma asperellum,especially isolated from marine algae,has contributed a number of new terpenes and nitrogen-bearing compounds,encouraging our continuous efforts to further explore them.Consequently,three new nitrogen-containing secondary metabolites,including cyclo(L-5-MeO-Pro-L-5-MeO-Pro)(1),5'-acetoxy-deoxycyclonerin B(2),and 5'-acetoxy-deoxycyclonerin D(3)were isolated from the marine alga-derived endophytic fungus Trichoderma asperellum A-YMD-9-2.Their structures and relative configurations were fully elucidated through spectroscopic techniques,mainly including 1D/2D NMR and MS.The absolute configurations of 1 and 2 were ascertained on the basis of X-ray diffraction(Cu Kα radiation)and ECD data,respectively.The isolation of these new nitrogen-bearing compounds adds to the structural diversity of marine algicolous Trichoderma spp.,and they display potent inhibition against some marine phytoplankton species.