A New Synthetic Method for the Preparation of α,β-Didehydroamino Acid Derivatives by Means of a Wittig-Type Reaction. Syntheses of (2S, 4S)- and (2R, 4R)-4-Hydroxyprolines

Abstract

Ethyl N-Boc- and N-Z-α-tosylglycinates were reacted with a variety of aldehydes in the presence of tributylphosphine and a base to afford the corresponding α,β-didehydroamino acid derivatives with high (Z)-selectivity in good yields. Moreover, ethyl (4S)- and (4R)-2-(N-Boc-amino)-4,5-isopropylidenedioxy-2-pentenoates prepared by the present method were converted to (2S, 4S)- and (2R, 4R)-4-hydroxyprolines, respectively.

Solid-Phase Total Synthesis of Dehydrotryptophan-Bearing Cyclic Peptides Tunicyclin B, Sclerotide A, CDA3a, and CDA4a using a Protected β-Hydroxytryptophan Building Block

“…They used this method to prepare protected Z-dehydrotryptophan derivatives 1.61 in fair yields; however, the reaction was found to take 67 h to reach completion and required 3 equivalents of the α-tosylglycinate 1.60 (Scheme 1.24). 52 Scheme 1.24. A Wittig type reaction used to make dehydrotryptophan species by Kimura et al…”

α,β-Dehydroamino Acids

“…53 Cyclization leads to the six-membered ring of dideoxynojirimycine, a glucosidase inhibitor. Kinoshita 54 reported a Wittig-type reaction using N-protected a-tosyl glycine ester in the reaction with tributylphosphine, sodium carbonate as base and tetrabutyl ammonium bromide as phase-transfer catalyst to prepare the ylide. The in situ reaction with (R)-isopropylideneglyceraldehyde gave a,b-dehydroamino esters in yields of up to 94% and complete Z selectivity (Scheme 8).…”

Stereoselective Syntheses of (E)-α,β-Didehydroamino Acid and Peptide Containing Its Residue Utilizing Oxazolidinone Derivative

“…4 The latter procedure was successfully applied to the synthesis of optically active 4-hydroxyprolines. 5 On the contrary, there are few reports 6 concerning stereoselective synthesis of (E)-¡,¢-didehydroamino acid since its stereochemistry is not always thermodynamically favored, for example, 1) stereoselective elimination of hydrogen chloride from erythro-¢-chloro-¡-amino acid derived from threo-¢-hydroxy-¡-amino acid derivative, 6a 2) stereospecific dehydration of erythro-¢-hydroxy-¡-amino acid derivative using DAST [(diethylamino)sulfur trifluoride], 6b 3) formation of cyclic cis-sulfamidite starting from erythro-¢-hydroxy-¡-amino acid derivative and thionyl chloride, and subsequent elimination of sulfur dioxide, 6c 4) Suzuki coupling of ¢-bromo-¡,¢-didehydroamino acid derivative with monosubstituted boronic acid, 6d 5) stereospecific dehydration of erythro-¢-hydroxy-¡-amino acid derivative using Martin's sulfurane [diphenylbis (1,1,1,3,3,3-hexafluoro-2-phenyl-2-propyl)sulfurane], 6e 6) stereospecific dehydration of threo-¢-hydroxy-¡-amino acid derivative with EDC [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide], 6f 7) oxidation of 3-S-benzylthioamino acid derivative to the sulfoxide, followed by thermolysis to form ¡,¢-didehydroamino acid. Although enantiomerically pure ¢-hydroxy-¡-amino acid derivative or ¢-bromo-¡,¢-didehydroamino acid derivative is required for preparation of the starting material as mentioned above, 3b,6 we now wish to report a new and effective stereoselective synthesis of (E)-¡,¢-didehydroamino acid derivative 1 via cis-4,5-oxazolidinone derivative 2 starting from methyl N-Boc-N-phenoxycarbonylglycinate 3f and a variety of aldehydes 4 according to retrosynthetic analysis as shown in Scheme 1.…”

“…Next, compound 10 was reacted with 1.2 molar equivalents of TBDPS-Cl in the presence of 3 molar equivalents of imidazole at room temperature for 4 h in dimethylformamide (DMF) to afford O-protected product 11 in 80% yield. Hydrogenation of the resulting compound 11 over 20% Pd(OH) 2 carbon in EtOH under hydrogen atmosphere at room temperature for 10 h took place stereospecifically from the less hindered side due to the bulky TBDPSoxymethyl substituent at position 5 to afford exclusively cis 3,5-disubstituted £-lactone derivative 12 as a single isomer in 89% yield, 5 whereas in the case of longer (overnight) reaction time, a mixture of cis and trans isomers was obtained in 62% and 13% yields, respectively. N-Deprotection of the resulting compound 12 by trifluoroacetic acid (TFA) at 0°C to room temperature for 1 h in dichloromethane and subsequent coupling reaction with 1.1 molar equivalents of N-(benzyloxycarbonyloxy)succinimide (Z-ONSu) in the presence of 3 molar equivalents of triethylamine (TEA) at 0°C to room temperature for 2 h in THF afforded the desired compound 7 in 80% yield.…”