- Total Synthesis of L-156,373 and an oxoPiz Analogue via a Submonomer Approach
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The first chemical synthesis of L-156,373 (1), a potent oxytocin receptor antagonist isolated from Streptomyces silvensis, is reported. Assembly of the unusual d-Piz-l-Piz dipeptide subunit was achieved through a sequential electrophilic amination-acylati
- Elbatrawi, Yassin M.,Kang, Chang Won,Del Valle, Juan R.
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supporting information
p. 2707 - 2710
(2018/05/22)
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- Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic γ-glutamyldiaminopimelic acid derivatives
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N-Acyl-γ-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C12-γ-d-Glu-DAP. Analogues with glutaric or γ-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopimelic acid, l- or d-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the d-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.
- Agnihotri, Geetanjali,Ukani, Rehman,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Balakrishna, Rajalakshmi,Wang, Xinkun,David, Sunil A.
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p. 1490 - 1510
(2011/04/24)
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- Synthesis of (R)- and (S)-(glu)Thz and the Corresponding Bisthiazole Dipeptide of Dolastatin 3
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Dolastatin 3 (1) has been reported to be a cyclic pentapeptide containing two thiazole amino acids, (gly)Thz (2) and (gln)Thz (3).The syntheses of (R)- and (S)-(glu)Thz (8a,b) and (glu)Thz-(gly)Thz (11a,b) derivatives suitable for elaboration to dolastatin 3 are described.A key feature of the (glu)Thz syntheses is the selective thiation of a primary amide with Lawesson's reagent in the presence of ester and urethane functionalities.
- Kelly, Robert C.,Gebhard, I.,Wicnienski, N.
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p. 4590 - 4594
(2007/10/02)
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