An improved synthesis of dioxindole-3-propionic acid and some transformations of the C-3 hydroxyl group

Labroo, Rita; Labroo, Virender M.; King, Michael M.; Cohen, Louis A.

doi:10.1021/jo00011a035

“…Since the ester moiety of 8 is located on the endo face of this concave skeleton, we thought if the ester could participate in this reaction, the intramolecular nucleophilic attack of the carbonyl oxygen of ester moiety at the C3 position of the intermediate 20 would give the desired spirolactone product. However, established methods such as the use of NBS,– t ‐BuBr/DMSO, NaI/H 2 O 2 , Ms 2 O/DMSO, (COCl) 2 /DMSO, or TTN, gave no reaction or low yield. Pleasingly, after extensive experimentation, we found that treatment of 8 with NCS in t ‐BuOH/H 2 O provided lactone 7 as a single diastereoisomer.…”

Section: Figurementioning

confidence: 99%

A Ten‐Step Total Synthesis of Speradine C

Liu

¹

,

Chen

²

,

Yuan

³

et al. 2019

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The first total synthesis of speradine Ch as been achieved in only ten steps from ac ommercially available 4bromoindole.Salient features of the work are the formation of four rings through three cyclizations,n amely ab ioinspired [3+ +2] annulation to form the C/D rings,a nN CS-mediated oxidation to construct the Ering, and aR u-catalyzed ketohydroxylation to assemble the Fring. This work highlights how strategic ring constructions can streamline the synthesis of polycyclic compounds. Scheme 1. Retrosynthetic analysis of speradine C.Scheme 2. Synthesis of tetracycle 9.THF = tetrahydrofuran, DMF = N,N-dimethylformamide, Tf = trifluoromethanesulfonyl, LiHMDS = lithium hexamethyldisilazide.Scheme 3. Proposed mechanism for the formation of 9a-c.

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“…Since the ester moiety of 8 is located on the endo face of this concave skeleton, we thought if the ester could participate in this reaction, the intramolecular nucleophilic attack of the carbonyl oxygen of ester moiety at the C3 position of the intermediate 20 would give the desired spirolactone product. However, established methods such as the use of NBS,– t ‐BuBr/DMSO, NaI/H 2 O 2 , Ms 2 O/DMSO, (COCl) 2 /DMSO, or TTN, gave no reaction or low yield. Pleasingly, after extensive experimentation, we found that treatment of 8 with NCS in t ‐BuOH/H 2 O provided lactone 7 as a single diastereoisomer.…”

Section: Figurementioning

confidence: 99%

A Ten‐Step Total Synthesis of Speradine C

Liu

¹

,

Chen

²

,

Yuan

³

et al. 2019

View full text Add to dashboard Cite

The first total synthesis of speradine Ch as been achieved in only ten steps from ac ommercially available 4bromoindole.Salient features of the work are the formation of four rings through three cyclizations,n amely ab ioinspired [3+ +2] annulation to form the C/D rings,a nN CS-mediated oxidation to construct the Ering, and aR u-catalyzed ketohydroxylation to assemble the Fring. This work highlights how strategic ring constructions can streamline the synthesis of polycyclic compounds.

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“…They were obtained in 64-82% total yield by oxidation of Z-L-tryptophan 8 with DMSO in the presence of t-BuBr [44,45], as mixtures with a moderate amount of the corresponding brominated derivative (X = Br), when R 2 = H, indicating that electrophilic bromine was released in the medium. In order to avoid bromination of the aromatic ring, attempts using DMSO activated with methanesulfonic anhydride [46] or oxalyl chloride [47], were performed and led to very low yields (ca 10%) in 9a and 10a (X = H).…”

Section: Chemistrymentioning

confidence: 99%

Structure-based design of human immuno- and constitutive proteasomes inhibitors

Richy

¹

,

Sarraf

²

,

Maréchal

³

et al. 2018

European Journal of Medicinal Chemistry

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Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines.

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An improved synthesis of dioxindole-3-propionic acid and some transformations of the C-3 hydroxyl group

Cited by 30 publications

References 5 publications

A Ten‐Step Total Synthesis of Speradine C

A Ten‐Step Total Synthesis of Speradine C

A Ten‐Step Total Synthesis of Speradine C

Structure-based design of human immuno- and constitutive proteasomes inhibitors

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