Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments.

Divergent total syntheses of binding pocket and peripherally modified tetrachlorovancomycins, a non-native synthetic glycopeptide, and their evaluation are disclosed. Central to the approach is the synthesis of a single late-stage intermediate that bears a residue 4 thioamide ([Ψ[C(═S)NH]Tpg]tetrachlorovancomycin (), LLS 15 steps, 14% overall) as a precursor to either of two key pocket modifications and their pairing with any combination of two peripheral modifications conducted without protecting groups. A stereochemical simplification achieved by the addition of two aryl chlorides removes two synthetically challenging atropisomer centers in native glycopeptides and streamlines the synthesis.

Tetrachlorovancomycin: Total Synthesis of a Designed Glycopeptide Antibiotic of Reduced Synthetic Complexity.

A technically straightforward total synthesis of a new class of vancomycin analogues of reduced synthetic complexity was developed that provided tetrachlorovancomycin (, LLS = 15 steps, 15% overall yield) and its precursor aglycon (nearly 20% overall yield). The class retains all the intricate vancomycin structural features that contribute to its target binding affinity and selectivity, maintains the antimicrobial activity of vancomycin, and achieves the simplification by an unusual addition, not removal, of benign substituents to the core structure. The modification, accomplished by addition of two aryl chloride substituents to provide , permitted a streamlined total synthesis of the new glycopeptide antibiotic class by removing the challenges associated with CD and DE ring system atropisomer stereochemical control.

Divergent Total Synthesis and Characterization of Maxamycins.

A new streamlined and scaled divergent total synthesis of pocket-modified vancomycin analogs is detailed that provides a common late-stage intermediate [Ψ[C(═S)NH]Tpg]vancomycin (LLS = 18 steps, 12% overall yield, >5 g prepared) to access both existing and future pocket modifications. Highlights of the approach include an atroposelective synthesis of [Ψ[C(═S)NH]Tpg]vancomycin aglycon (), a one-pot enzymatic glycosylation for direct conversion to [Ψ[C(═S)NH]Tpg]vancomycin (), and new powerful methods for the late-stage conversion of the embedded thioamide to amidine/aminomethylene pocket modifications. Incorporation of two peripheral modifications provides a scalable total synthesis of the maxamycins, all prepared from aglycon without use of protecting groups.

Intramolecular Singlet Fission in Pentacene Oligomers via an Intermediate State.

Intramolecular singlet fission (iSF) is an efficient strategy of multiexciton generation via a singlet exciton splitting into a correlated triplet pair in one organic molecule with more than two chromophores. Propeller-shaped iptycene-linked triisopropylsilyl(TIPS)-ethynyl functionalized pentacene oligomers (pent-monomer, pent-dimer, and pent-trimer) were synthesized, and the iSF dynamics of pent-dimer and -trimer were monitored by a visible-near-IR transient absorption (TA) spectroscopy. Quantum yields of the triplet pair, ∼80%, of both estimated by near-IR TA spectral analysis are in good agreement with the results of global analysis and triplet sensitization experiments.

Didehydroisobenzofuran: A New Reactive Intermediate for Construction of Isoacenofuran.

An efficient generation method of didehydroisobenzofuran, a new heteroaryne species, was developed by bromine/lithium exchange of the dibromoisobenzofuran. The reactive intermediate, thus generated, was trapped by appropriate arynophile to give the [2+2], [2+3], and [2+4] cycloadducts, respectively. Moreover, the reaction could be applied to the syntheses of isoanthracenofurans (anthra[2,3-c]furans), a new class of heteroacenes, with isoelectoronic structure to the corresponding acenoheteroles (anthra[2,3-b]furans).