Total Synthesis of 6-Deoxydihydrokalafungin, a Key Biosynthetic Precursor of Actinorhodin, and Its Epimer

In this article, we report the total synthesis of 6-deoxydihydrokalafungin (DDHK), a key biosynthetic intermediate of a dimeric benzoisochromanequinone antibiotic, actinorhodin (ACT), and its epimer, epi-DDHK. Tricyclic hemiacetal with 3-siloxyethyl group was subjected to Et3SiH reduction to establish the 1,3-cis stereochemistry in the benzoisochromane, and a subsequent oxidation/deprotection sequence then afforded epi-DDHK. A bicyclic acetal was subjected to AlH3 reduction to deliver the desired 1,3-trans isomer in an approximately 3:1 ratio, which was subjected to a similar sequence to that used for the 1,3-cis isomer that successfully afforded DDHK. A semisynthetic approach from (S)-DNPA, an isolable biosynthetic precursor of ACT, was also examined to afford DDHK and its epimer, which are identical to the synthetic products.

Understanding the binding properties of phosphorylated glycoluril-derived molecular tweezers and selective nanomolar binding of natural polyamines in aqueous solution

Selective nanomolar binding of biological polyamines to a novel glycoluril-derived molecular tweezer is reported. The high selectivity over their biosynthetic precursor may be of interest, as elevated polyamine levels are linked to several diseases.

Streptococcus pneumoniae, S. mitis, and S. oralis produce a phosphatidylglycerol-dependent, ltaS-independent glycerophosphate-linked glycolipid

Lipoteichoic acid (LTA) is a cell surface polymer of Gram-positive bacteria. LTA participates in host-microbe interactions including modulation of host immune reactions. It was previously reported that the major human pathogen Streptococcus pneumoniae and the closely related oral commensals S. mitis and S. oralis produce Type IV LTAs. Herein, using liquid chromatography/mass spectrometry (LC/MS)-based lipidomic analysis, we found that in addition to Type IV LTA biosynthetic precursors, S. mitis, S. oralis, and S. pneumoniae also produce glycerophosphate (Gro-P)-linked dihexosyl-diacylglycerol (DAG), which is a biosynthetic precursor of Type I LTA. Mutants in cdsA and pgsA produce dihexosyl-DAG but lack (Gro-P)-dihexosyl-DAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. S. mitis, but neither S. pneumoniae nor S. oralis, encodes an ortholog of the PG-dependent Type I LTA synthase, ltaS. By heterologous expression analyses, we confirmed that S. mitis ltaS confers poly-(Gro-P) synthesis in both Escherichia coli and Staphylococcus aureus, and that S. mitis ltaS can rescue the severe growth defect of a S. aureus ltaS mutant. However, despite these observations, we do not detect a poly-(Gro-P) polymer in S. mitis using an anti-Type I LTA antibody. Moreover, (Gro-P)-linked dihexosyl-DAG is still synthesized by a S. mitis ltaS mutant, demonstrating that S. mitis LtaS does not catalyze the transfer of Gro-P from PG to dihexosyl-DAG. Finally, a S. mitis ltaS mutant has increased sensitivity to human serum, demonstrating that ltaS confers a beneficial but currently undefined function in S. mitis. Overall, our results demonstrate that S. mitis, S. pneumoniae, and S. oralis produce a (Gro-P)-linked glycolipid via a PG-dependent, ltaS-independent mechanism.ImportanceLTA is an important cell wall component synthesized by Gram-positive bacteria. Disruption of LTA production can confer severe physiological defects and attenuation of virulence. We report here the detection of a biosynthetic precursor of Type I LTA, in addition to the previously characterized Type IV LTA, in the total lipid extracts of S. pneumoniae, S. oralis, and S. mitis. Our results indicate that a novel mechanism is responsible for producing the Type I LTA intermediate. Our results are significant because they identify a novel feature of S. pneumoniae, S. oralis, and S. mitis glycolipid biology.

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

The application of oxidative dimerization for the biomimetic synthesis of balsaminone A and ellagic acid is described. Balsaminone A is synthesized via the oxidative dimerization of 1,2,4-trimethoxynaphthalene under anhydrous conditions using CAN, PIDA in BF3 ·OEt2 or PIFA in BF3 ·OEt2 in 7–8% yields over 3 steps. Ellagic acid is synthesized from its biosynthetic precursor gallic acid, in 83% yield over 2 steps.

Diterpenes with bicyclo[2.2.2]octane moieties from the fungicolous fungus Xylaria longipes HFG1018

Xylarilongipins A and B, along with their biosynthetic precursor hymatoxin L, were isolated from the culture broth of the fungicolous fungus Xylaria longipes HFG1018 inhabiting in the medicinal fungus Fomitopsis betulinus.

Direct transformation of i-steroid methyl ethers in 6-ketones: the use in the synthesis of brassinosteroids

A one-step method for the transformation of 3α,5-cyclo-6β-methyl ethers of steroids into the corresponding 3α,5-cyclo-6-ketones under the action of methyl (trifluoromethyl) dioxirane has been developed. The possibilities of the method have been demonstrated by preparing 3-dehydrotesterone, the biosynthetic precursor of brassinolide.

Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Enantioselective Total Synthesis of Mavacuran Alkaloids

We report the enantioselective total syntheses of mavacurans alkaloids, (+)-taberdivarine H, (+)-16-hydoxymethyl-pleiocarpamine, (+)-16-epi-pleiocarpamine, and their postulated biosynthetic precursor 16-formyl-pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, we explored an oxidative coupling approach from the geissoschizine framework to form the N1-C16 bond. Quaternization of the aliphatic nitrogen was key to achieve the oxidative coupling induced by KHMDS/I₂sinceit hides the nucleophilicity of the aliphatic nitrogen and locks the required cis conformation.