Stereoselective Synthesis of (2R,5R)- and (2S,5R)-5-Hydroxylysine

Abstract

A stereoselective synthesis of (2S,5R)‐5‐hydroxylysine (1) and (2R,5R)‐5‐hydroxylysine (17), based on a concept involving Williams glycine template methodology and (R)‐hydroxynitrile lyase for the introduction of chirality at the α‐position and the side‐chain, respectively, is described. This strategy offers an expeditious route towards orthogonally protected 5‐hydroxylysines.

Structure–Odor Relationships of (Z)-3-Alken-1-ols, (Z)-3-Alkenals, and (Z)-3-Alkenoic Acids

“…The 3-alkyn-1-ols that were required as intermediates for the subsequent synthetic steps were successfully obtained following the method reported by Heath et al and Argenti et al , The ( Z )-3-alken-1-ols were generated therefrom by selective hydrogenation of the corresponding 3-alkyn-1-ol with poisoned Lindlar’s catalyst, and the corresponding ( Z )-3-alkenals were obtained via mild oxidation of the corresponding ( Z )-3-alken-1-ols with Dess–Martin periodinane as oxidizing agent. , The respective ( Z )-3-alkenoic acids were synthesized following two different methods. Compounds 17 and 22 – 24 were obtained by oxidation with H 5 IO 6 /CrO 3 in wet MeCN according to the procedure of Zhao et al, whereas compounds 18 – 21 were synthesized by applying a Pinnick oxidation reaction (Figure A–C). − …”

“…It was then filtered through a glass frit, and the filtrate was washed with saturated aqueous NaHCO 3 solution containing Na 2 S 2 O 3 (25%) (3.5 mL/mmol alcohol). The resulting clear solution was dried over MgSO 4 and filtered, and the solvent was removed under reduced pressure to give the corresponding ( Z )-3-alkenal as a colorless to pale yellow oily liquid . ( Z )-3-Decenal and ( Z )-3 dodecenal were purified by prep-HPLC.…”

Synthesis of glycosylated 5-hydroxylysine, an important amino acid present in collagen-like proteins such as adiponectin

“…Van den Nieuwendijk et al 47 have also used a stereoselective alkylation of Willams' glycine template to prepare 5-HL using chiral iodides as the electrophiles.…”

Biological Relevance and Synthesis of C-Substituted Morpholine Derivatives

“…In addition, (2R,5R)-5-hydroxylysine was obtained starting from 149a. 63 Finally, the total synthesis of (+)-hypusine dihydrochloride (175) was achieved starting from both 149a and 149b. 64…”