Nitro-polyols via Pyridine Promoted CC Cleavage of 2‑Nitroglycals. Application to the Synthesis of (−)-Hyacinthacine A1

A mild and convenient transformation for the synthesis of nitro-polyols is described. The nitro-polyol derivatives were prepared either from 2-nitroglycals via a pyridine-promoted scission of the carbon–carbon double bond or from glycals via a sequential nitration–scission procedure. The generated nitro-polyols could undergo a stereoselective Michael addition reaction. The utility of the addition products was exemplified by the concise synthesis of (−)-hyacinthacine A1 and 7a-<i>epi</i>-(−)-hyacinthacine A1

Efficient synthesis of (2<i>S</i>)-<i>tert</i>-butyl 2-(2-bromopropanamido)-5-oxo-5-(tritylamino)pentanoate as a precursor of PET radiotracer [¹⁸F]FPGLN

<p>This study describes a convenient protocol for the synthesis of (2<i>S</i>)-<i>tert</i>-butyl 2-(2-bromopropanamido)-5-oxo-5-(tritylamino)pentanoate, which can serve as an appropriate precursor of (2<i>S</i>)-5-amino-2-(2-[¹⁸F]fluoropropanamido)-5-oxopentanoic acid (<i>N</i>-(2-[¹⁸F]fluoropropionyl)-L-glutamine, [¹⁸F]FPGLN) for tumor positron emission tomography imaging. Five-step synthesis starting from L-glutamine provided the desired precursor with high yields. In addition, a simple method for the preparation of [¹⁸F]FPGLN from this easily available precursor was developed using a two-step ¹⁸F-labeling strategy.</p

Lewis Acid Catalyzed Intramolecular [3 + 2] Cross Cycloadditions of Cobalt-Alkynylcyclopropane 1,1-Diesters with Carbonyls for Construction of Medium-Sized and Polycyclic Skeletons

A Lewis acid catalyzed intramolecular [3 + 2] cross cycloaddition of cobalt-alkynylcyclopropane 1,1-diesters with carbonyls has been successfully developed. Together with simple and efficient postcycloadditions of the cobalt-alkyne moiety, a general and efficient strategy for construction of structurally complex and diverse medium-sized skeletons and related polycycles was supplied successfully

Stereocontrolled Synthesis of 2‑Deoxy‑<i>C</i>‑glycopyranosyl Arenes Using Glycals and Aromatic Amines

An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective preparation of the challenging β-<i>C</i>-glycosyl arenes by the anomerization of α-<i>C</i>-glycosides using HBF₄ is also described. This protocol has a broad substrate scope and a wide functional-group tolerance. It can be used for the gram-scale preparation of 3-oxo-<i>C</i>-glycosides, which are versatile substrates for the preparation of many biologically important <i>C</i>-glycosides

Total Synthesis and Determination of the Absolute Configuration of Vinylamycin

The absolute configurations of the three unknown chiral centers in vinylamycin were predicted according to the structural comparison with microtermolide A and rakicidin A, and then total syntheses of vinylamycin were applied to determine the three unknown chiral centers as 14<i>R</i>, 15<i>R</i>, and 16<i>S</i>

α‑Alkylation of Chiral Sulfinimines for Constructing Quaternary Chiral Carbons by Introducing Removable Directing Groups

This study developed a facile and efficient synthetic strategy to construct quaternary chiral centers at the α-position of imines and ketones. High regioselectivity and diastereoselectivity were achieved through the synergetic effect of electron-withdrawing directing groups and <i>N</i>-<i>tert</i>-butyl sulfinamide as chiral auxiliaries. Either of them could be removed under the optimized conditions without any epimerization

Total Syntheses and Biological Activities of Vinylamycin Analogues

Natural depsipeptide vinylamycin was reported to be an antibiotic previously. Herein we report vinylamycin to be active against K562 leukemia cells (IC₅₀ = 4.86 μM) and be unstable in plasma (<i>t</i>_1/2 = 0.54 h). A total of 24 vinylamycin analogues with modification of the OH group and chiral centers were generated via a combinatorial approach. The lead compound <b>1a</b> was subsequently characterized as having the following: no antimicrobial activity, significantly higher plasma stability (<i>t</i>_1/2 = 14.3 h), improved activity against K562 leukemia cells (IC₅₀ = 0.64 μM), and up to 75% cell inhibition without significant toxicities in K562 cells xenograft zebrafish model. Furthermore, compound <b>1a</b> maintained its activity against the breast cancer cell line MCF-7 under hypoxic conditions. In comparison, the activity of gemcitabine in the same hypoxic in vitro model of MCF-7 cells was 15-fold lower. Therefore, the present results demonstrate that <b>1a</b> has great potential as an anticancer agent