Total synthesis of the azolemycins

Abstract

The first total syntheses of newly isolated polyazole natural products azolemycins A-D, along with the synthesis of the tetra-oxazole non-natural analogue, are described.

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

“…The structure was also independently confirmed by total synthesis (Figure 11). 197 No definitive bioactivity has been found for the azolemycins with only modest anti-proliferative activity being observed. 197 …”

Evaluation of health benefits of sea lamprey (Petromyzon marinus) isolates using in vitro antiinflammatory and antioxidant assays

“…Furthermore, protons H-2’’, H-3’’, H-4’’, H-5’’, and H-6’’ were correlated to C-2’’ (δ C 53.3), C-3’’ (δ C 39.7), C-4’’ (δ C 24.0), C-5’’ (δ C 21.9) and C-6’’ (δ C 20.7), respectively, in its HSQC spectrum (Figs A.10 and A.11 in S1 File ). The HMBC correlation of methine group at H-2’’ to C-1’’ (δ C 175.6), C-3’’ (δ C 39.7) and C-4’’ (δ C 24.0), H-4’’ to C-2’’ (δ C 53.3), C-5’’ (δ C 21.9), and C-6’’ (δ C 20.7) further supported the evidence of a 2-substituted-4-methylpentanoic acid subunit [(CH 3 ) 2 CHCH 2 CH-COOH] in compound 1 (Figs A.10 and A.11 in S1 File ) [ 16 , 17 ].…”

“…The 1 H- 1 H COSY correlations of protons H-2’ to H-3’, H-3’ to H-4’a, H-4’b, H-5’, and H-6’ along with HOMODEC NMR data indicated the presence of a 2-substituted-3-methylpentanoic acid subunit [CH 3 CH 2 CH(CH 3 )CH-COOH] in the molecule ( Fig 2 ) (Figs A.5-A.7 in S1 File ). Furthermore, 1 H- 1 H COSY NMR correlations of protons H-2’’ to H-3’’ and H-4’’ and H-4’’ to H-5’’ and H-6’’ along with HOMODEC NMR data supported a 2-substituted-4-methylpentanoic acid subunit [(CH 3 ) 2 CHCH 2 CH-COOH] in the molecule ( Fig 2 ) (Figs A.5-A.7 in S1 File ) [ 16 , 17 ].…”

“…Purification of subfraction I (160 mg) was accomplished by HPLC by eluting the column with water:methanol (95:5, v/v , 3 mL/min) under isocratic condition. This yielded compound 1 (40 mg, 29.9 min, Figs 1 and 2 , Figs A.1-A.14 in S1 File ) [ 16 – 19 ], 3-phenyllactic acid (87 mg, 31.4 min, Fig 1 , Figs B.1-B5 in S1 File ) and pyruvic acid (26 mg, 40.9 min, Fig 1 , Figs C.1-C.3 in S1 File ), respectively [ 20 ]. Similarly, purification of subfraction II (150 mg) by HPLC under identical conditions afforded proline (64 mg, 36.9 min, Figs D.1-D.5 in S1 File ), serine (19 mg, 39.9 min, Fig 1 , Figs E.1-E.4 in S1 File ) and 3-hydroxybutyric acid (52 mg, 45.6 min, Fig 1 , Figs F.1-F.3 in S1 File ), respectively [ 20 ].…”

NMR-based assignment of isoleucinevs.allo-isoleucine stereochemistry

“…2 1 H, 13 C and 15 N NMR spectrometry can also be used to calculate the level of epimerisation, either via chiral derivatisation or with a chiral shift reagent. 3 Recently, during the structural assignment 4 and synthesis 5 of the azolemycins, we noted that the 1 H NMR spectrum of the isoleucine portion of the natural product was significantly different from its alloisoleucine diastereoisomer.…”