Chemoenzymatic Synthesis of Triazololactams Structurally Related to Pancratistatin

Abstract

Four tricyclic lactams that structurally resemble alkaloids with the pancratistatin skeleton were synthetized from bromobenzene by a chemoenzymatic strategy. The sequence involved enzymatic dihydroxylation, efficient stereodirected oxidation of double bonds, inter‐ or intramolecular Huisgen cycloaddition, and a solvent‐free cyclization. The complex structures were obtained in high chemical and optical purity and may be good candidates for biological testing.

Readily accessible azido-alkyne-functionalized monomers for the synthesis of cyclodextrin analogues using click chemistry

“…The regiochemical outcome obtained for the epoxide opening is in agreement with the literature Organic & Biomolecular Chemistry Paper reports for the opening of allylic cyclohexene oxides of type 10 and 6, which takes place exclusively at the allylic position for a number of nucleophiles (alcohols, amines, azides, hydrides, and thiols). [25][26][27][28][29][30][31] The removal of the acetonide group under acidic conditions using CuCl 2 •2H 2 O 22a afforded the diol in 80% yield. Finally, selective mesylation at the allylic position, followed by azide displacement gave 2b in 88% yield for the two-step sequence, representing an overall yield of 27% from cis-diol 1.…”

“…Treatment of intermediate 10 with sodium azide in a ternary solvent mixture 26 gave an azido alcohol in an excellent yield, which after treatment with CuCl 2 •2H 2 O afforded the corresponding triol in 80% yield. 31 This compound was reacted with propargyl bromide under basic conditions to give 3 in 60% isolated yield, along with small amounts (less than 10%) of by-products resulting from mono-and di-propargylation of the other secondary alcohols.…”

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

“…Finally hydroxylation with tBuO 2 H in THF at this 7 position completed the synthesis of (+)-pancratistatin 241 in a 62% yield (Scheme 41). ix) Miscellaneous: Finally, in this section on pancratistatin syntheses, a paper describing the chemoenzymatic synthesis of triazololactams somewhat structurally related to pancratistatin, by de la Sovera et al should be noted [45]. g) Phenanthridine-scaffold alkaloids i) Synthesis of ismine, by Chen and co-workers: Chen and coworkers developed a short and efficient synthesis for the neuroprotective and antifungal Amaryllidaceae alkaloid ismine 257 starting from 2-bromo-4,5-(methylenedioxy) benzoic acid 253 [46].…”

Chemoenzymatic Synthesis of Hygromycin Aminocyclitol Moiety and its C2 Epimer

“…Initial efforts of Hudlicky et al since the early nineties of the last century have developed into a full stereodivergent strategy that has been exploited around the world to render a wide diversity of this nitrogen containing polyols . Recently, we have targeted the synthesis of more complicated structures bearing a cyclitol core such as pancratistatin analogues and linear molecules inspired in the hygromycin A skeleton …”