Synthesis of the Carboline Disaccharide Domain of Shishijimicin A

Abstract

A synthetic route to the carboline disaccharide domain (2) of shishijimicin A (1) has been developed. The convergent synthesis relies on a novel application of the Reetz–Müller-Starke reaction to form the central, sulfur-bearing quaternary carbon center and addition of the carboline structural motif as a dianion to a disaccharide aldehyde fragment.

One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides

“…In the first step, TMSOTf promotes the highly diastereoselective (TMS) 2 S ring-opening of anhydrosugar A following a S N 2-type mode [ 6 ]. In a second step, addition of the resulting α-thioglycoside B to the TMSOTf-activated carbonyl compound affords the stabilized α-thio carbocation D via thioacetal C [ 15 , 16 , 17 , 18 ]. The subsequent interception of this carbocation by a second molecule of α-thioglycoside B affords the dithioacetal-α,α-diglycoside E after aqueous work-up.…”

Fischer Reaction with 2‐Perfluoroalkylated Cyclic Imines ― An Efficient Route to 2‐Perfluoroalkyl‐Substituted Tryptamines and Their Derivatives and Homologues

“…General Methods: 1D NMR ( 1 H, 19 F, and 13 C) spectra were obtained with 400 MHz spectrometers. Chemical shifts are reported in parts per million downfield from tetramethylsilane.…”

“…Deuterated solvent peaks were used as internal references: [D]chloroform at δ = 7.27 and 77.0 ppm, [D 6 ]DMSO at δ = 2.50 and 39.5 ppm, and [D 6 ]acetone at δ = 2.04 and 29.8 or 206.7 ppm. Chemical shifts for 19 F NMR spectroscopic data were referenced to CFCl 3 (δ = 0.0 ppm) or PhCF 3 (δ = -63.90 ppm). High-resolution mass spectrometry (HRMS) was carried out using a MicroTOF-Q instrument.…”

“…Spectral data are consistent with those reported in the literature. [19] General Procedure for the Acylation of Hydrazone: The appropriate hydrazone hydrochloride (5 mmol; 3b: 1.48 g, 3e: 1.38 g) was dissolved in pyridine (5 mL), and acetic anhydride (5.5 mmol, 0.52 mL) was added to the cooled solution. The reaction mixture was stirred for 12 h at ambient temperature.…”

Total Synthesis of Shishijimicin A

“…Finally, 6 was traced back to tryptamine derivative 8, while 7 was disconnected into its obvious monosaccharide units 9 (acceptor) and 10 (donor) as key building blocks. 16 The synthesis of the required enediyne thioacetate precursor 4 from key building block 5 13 proceeded as shown in Scheme 2. This route represents a streamlined and significantly improved version of the original synthesis of the benzoate counterpart of 4 employed in the total synthesis of calicheamicin γ 1 I (19 steps, 21% overall yield from 5 vs 21 steps, 1.7% overall yield from 5).…”