Mild and Efficient Lewis Acid-Promoted Detritylation in the Synthesis of N-Hydroxy Amides:  A Concise Synthesis of (−)-Cobactin T

Abstract

An efficient, high-yielding Lewis acid promoted deprotection of O-trityl hydroxylamine derivatives is described. A range of acid-labile protecting groups, such as N-Boc and O-TBS, were tolerated under these mild conditions. The present method is applicable to the synthesis of a broad range of hydroxylamine derivatives, including N-hydroxy amides (hydroxamic acids), N-hydroxy sulfonamides, and N-hydroxy ureas, which often exhibit significant biological activities. An application of this methodology for a concise synthesis of (-)-Cobactin T (18) is also demonstrated.

Synthesis and Structural Study of Tetravalent (Zr4+, Hf4+, Ce4+, Th4+, U4+) Metal Complexes with Cyclic Hydroxamic Acids

“…Subjecting cyclohexanone to a similar ring‐expansion reaction did not allow us to isolate 2 H in appreciable amounts, in agreement with the literature 14b. Therefore, to prepare compound 2 H, we decided to adapt the multistep route developed for making the amino‐functionalized optically active analog 4 H in the context of the synthesis of (–)‐cobactin T 15. Accordingly, 5‐pentenoic acid 7 was treated first with trityl‐protected hydroxylamine 8 to produce 9 in 75 % yield (Scheme ).…”

Antimalarial and antileishmanial activities of histone deacetylase inhibitors with triazole-linked cap group

“…Deprotection of O -trityl- p-N,N -dimethylanilyltriazolyloctahydroxamate 6 (186 mg, 0.32 mmol) under unoptimized conditions25 used BF 3 •OEt 2 (0.08 ml) without thioanisole in 4:1 CHCl 3 :MeOH (15 ml) at r.t. for 3 h. The reaction was poured into 1:1 H 2 O:CHCl 3 (100 mL) and the aqueous layer extracted with CHCl 3 (50 mL). The combined organic layer was washed with brine (50 mL), then dried over Na 2 SO 4 and concentrated in vacuo .…”

Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue

“…The temperature and reaction time needed optimization for each chemotype to ensure complete conversion of PFB to TFPA. It was also important to monitor completion of the reaction using liquid chromatography massspectrometry analysis (LC-MS) and 19 F NMR as the starting PFB derivatives often exhibited identical retention times and were inseparable by chromatography. Lowering reaction temperature required longer reaction times resulting in formation of additional side products and a reduced yield.…”

“…For hydroxamate PRPs, detritylation of intermediates 27, 36, 42 and 50 (Schemes 2-5) was carried out using a Lewis acid mediated deprotection. [19] Protic acids commonly used for deprotection, such as trifluoroacetic acid and hydrochloric acid, were found to be incompatible in deprotection of intermediates containing TFPA moiety, resulting in a complex mixture of products (Scheme S3, D). Deprotection of Boc intermediates 28 and 44 (Schemes 2 and 4) required an ice-cooled reaction for 3-6 h. Longer reaction times or reactions at room temperature gave the previously reported benzimidazole cyclization side product as detected by LC-MS (Scheme S3, E).…”