Anisole → HCID 86739975, compound

HRID 2164539Notes

Reaction equation

HRID 2164539 reaction equation
[CH3:1][C@@H:2]([OH:115])[C@@H:3]1[NH:51][C:49](=[O:50])[C@H:48]([CH2:52][CH2:53][CH2:54][CH2:55][NH2:56])[NH:47][C:45](=[O:46])[C@H:44]([CH2:57][C:58]2[C:62]3[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=3[NH:60][CH:59]=2)[NH:43]C(=O)[C@H](CC2C=CC=CC=2)NC(=O)[C@H](CC2C=CC=CC=2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(CNC([C@@H](N)C)=O)=O)CSSC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@H](O)C)[NH:10][C:8](=[O:9])[C@H:7]([CH2:108][C:109]2C=CC=C[CH:114]=2)[NH:6][C:4]1=[O:5].[CH:116]1[CH:121]=[C:120]2[C:122]([C:124](O)(O)[C:125](=O)[C:119]2=[CH:118][CH:117]=1)=[O:123].C1(OC)C=CC=CC=1>>[N:6]12[CH2:114][CH2:109][CH2:108][C@H:7]1[C:8]([NH:10][C@H:124]([C:122]([NH:43][C@@H:44]([C:45]([NH:47][C@H:48]([C:49]([NH:51][C@H:3]([C:4]2=[O:5])[C@@H:2]([CH3:1])[OH:115])=[O:50])[CH2:52][CH2:53][CH2:54][CH2:55][NH2:56])=[O:46])[CH2:57][C:58]1[C:62]2[C:61](=[CH:66][CH:65]=[CH:64][CH:63]=2)[NH:60][CH:59]=1)=[O:123])[CH2:125][C:119]1[CH:118]=[CH:117][CH:116]=[CH:121][CH:120]=1)=[O:9]

Participants

4

Reactant 3

HCID 7519AnisoleHCID 10236NinhydrinHCID 1612970638916-34-6

Product 1

HCID 86739975HCID 86739975, compound

Procedure

After conventional solid-phase assembly beginning with 1 mmole of Boc-Phe-Merrifield resin (1% cross-linked), the protected peptide hydrazide, H-D-Trp-Lys(Cl-Z)-Thr(Bzl)-Pro-Phe-NHNH2, is cleaved from the support by treatment with hydrazine in methanol and isolated by a procedure described by D. F. Veber et al., Proceedings of the National Academy of Science, U.S.A., 75: 2636-2640, (1978). Without further purification, the hydrazide is converted to the azide, neutralized with triethylamine, and cyclized in DMF solution to yield the protected ninhydrin negative material, cyclo[Pro-Phe-D-Trp-Lys-(Cl-Z)-Thr(Bzl)]. When this protected ninhydrin negative material is hydrogenated at atmospheric pressure and room temperature over 10% Pd on charcoal, the compound, cyclo[Pro-Phe-D-Trp-Lys-Thr(Bzl)], is formed and found to be a very effective somatostatin antagonist. When, however, the protected crude ninhydrin negative material is deprotected by treatment with HF-anisole under standard conditions, as described by G. T. Engberg et al., Nature, 293: 222-223, (1981), and purified by preparative HPLC eluting with 10-55% gradient of CH3CN in 20% AcOH, the reaction yields the pure peptide, cyclo(Pro-Phe-D-Trp-Lys-Thr), which has somatostatin antagonist activity.

Workup

  1. customEngberg et al., Nature, 293: 222-223, (1981), and purified by preparative HPLC
  2. washeluting with 10-55% gradient of CH3CN in 20% AcOH

Sources & evidence

ORD record
ord-9407ca395b56447c9f7f5f18d683463a
Source dataset
uspto-grants-1985_03
Patent number
US04505897

Reaction notes

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