[Show abstract][Hide abstract] ABSTRACT: Our recent studies on the synthetic methodology of head to tail cyclization of linear peptides are summarized in this paper.
Ten cyclopeptides including six cyclopentapeptides as candidates of LHRH antagonists, two cyclopentapeptides, and two cycloheptapeptides
which were isolated from Chinese medicinal herbs were synthesized using an organic phosphorus reagent, DEPBT, and were selected
as model peptides for studying the factors that influence the cyclization yields. Our results show that the coupling reagent
choice and linear peptide sequence are the two most important considerations that determine the success or failure for a cyclization
reaction. Effects of different metal ions on the cyclization were also studied. The results suggest that Na+ is suitable for promoting the cyclization of linear pentapeptides while bigger Cs+ is better for promotion of the ring closure of linear heptapeptides. Application of Pac ester in thioester method for synthesis
of cyclopeptides was studied. N-protected amino acid and peptide thioesters with Pac group were readily purified in each step
of synthesis. The Pac group was easy to remove with zinc powder in acetic acid and its flexibility allows elongatation of
the peptide chain from either N-or C-terminal.
No preview · Article · Nov 2003 · Letters in Peptide Science
[Show abstract][Hide abstract] ABSTRACT: Six cyclic pentapeptides containing two or three non-protein amino acids have been synthesized by cyclization of linear precursors in dilute solution and characterized by TLC. HPLC, NMR, melting point. specific rotation etc. A total of 72 cyclization reactions were carried out to study the factors that influence head-to-tail cyclization: linear precursor sequence, coupling reagent, residue configuration, the proportion of DMAP additive, concentration, reaction temperature and reaction time. The cyclic pentapeptides will be modified by active moieties and evaluated as LHRH antagonists.
No preview · Article · Aug 2002 · Journal of Peptide Science
[Show abstract][Hide abstract] ABSTRACT: The host–guest complexation behaviour ofß-cyclodextrin 6-O-mono-2-naphthoate(1) and 6-[(N-2-naphthoyl-2-aminoethyl) amino]-6-deoxy-ß-cyclodextrin (2) have been studied by the circular dichroism method. The exciton coupling band of 1 suggests that two naphthoyl moieties are partly included in one ß-CD cavity. Host 1 could form a dimer in a more polar solvent and the dimer could be dissociated in a less polar solvent or by adding a guest. Solvent-induced, concentrationinduced, and guest-induced circular dichroism variations were examined. No exciton coupling was observed for host 2.
No preview · Article · Feb 2001 · Journal of Inclusion Phenomena
[Show abstract][Hide abstract] ABSTRACT: Supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to the chiral (E)-isomer (1E) via inclusion and sensitization by modified α-, β-, and/or γ-cyclodextrin derivatives, possessing benzoate (2a, 3a, 4a), isomeric phthalates (3b−d), and tethered benzamide (3e) chromophores, has been investigated in aqueous methanol solutions at varying temperatures. The photostationary-state 1E/1Z ratios obtained upon sensitization with 2−4 in 1:1 water−methanol reached 0.4−0.8, which are higher than the value of ca. 0.25 reported for sensitizations by conventional alkyl benzoates in hydrocarbon solvents, although the ratio was reduced to 0.2−0.4 in water or methanol. The sensitizations of 1Z by α- and γ-cyclodextrin benzoates (2a, 4a) with size-mismatched cavities gave 1E of poor enantiomeric excesses (ee's) smaller than 3 and 5%, respectively. In contrast, β-cyclodextrin derivatives (3a−e) afforded much higher ee's of up to 24%, depending on the solvent composition. Thus, the modification of cyclodextrin with a sensitizing group successfully enhanced the product through the excited-state supramolecular interaction within the cavity. Interestingly, the product ee's obtained with benzoate 3a and methyl phthalate 3b are not a simple function of either temperature or solvent, but are nicely correlated with the host occupancy or the percentage of occupied host. This means that the entropy factor plays an insignificant role in this supramolecular photochirogenesis system, which is in sharp contrast to the decisive role of entropy in the conventional (nonsupramolecular) counterpart performed in homogeneous solutions, where an inversion of product chirality by temperature variation is reported to occur.
No preview · Article · Oct 2000 · The Journal of Organic Chemistry
[Show abstract][Hide abstract] ABSTRACT: Two cyclopentapeptides cyclo(ProTyrLeuAlaGly)(1) and cyclo(AlaTyrLeuAlaGly)(2) isolated and identified from a Chinese medicinal herb were chosen as model cyclopeptides to evaluate a novel coupling reagent DEPBT (3-(diethoxy-phosphoryloxy-1,2,3-benzotriazin-4(3H)-one). DEPBT was used for synthesis of cyclic peptides in one-pot procedure. Compared with some other coupling reagents, the cyclization yields were satisfactory.
No preview · Article · Jul 2000 · Chemistry Letters
[Show abstract][Hide abstract] ABSTRACT: Host-guest complexation of β-cyclodextrin substituted by one 2-naphthoyl moiety (1) has been studied by the circular dichroism method. The exciton coupling band suggests that two naphthoyl moieties are partly included in one β-CD cavity (forming a dimer). Both solvent-induced and guest-induced circular dichroism variations are examined.
No preview · Article · Jan 1999 · Tetrahedron Letters
[Show abstract][Hide abstract] ABSTRACT: Novel α- and/or β-cyclodextrin benzoates (2α, 2β), methyl phthalate (3β), tethered benzamide (4β) and 2-naphthoate (5β) have been synthesized. The complex stability constants (Ks) of these cyclodextrin derivatives with a series of acyclic and cyclic hydrocarbons, and alcohols have been determined in water to reveal the role of the hydrophilic group in the guest molecule, and to evaluate the individual contribution of weak interactions involved in inclusion complexation by cyclodextrin. The free energy of complexation (–ΔG°) increases linearly to a certain limit with extending chain length or ring size (NC) of the guests, giving unit increments per methylene (–dΔG°/dNC). Interestingly, the unit increment obtained is independent of the host’s size or substituent introduced, but is a critical function of the guest type. Thus, a remarkably large –dΔG°/dNC value of 5.4 kJ mol–1 has been obtained for the cycloalkane series, whereas much smaller, but conventional, values have been recorded for cycloalkanols (3.3 kJ mol–1), alkanes (3.1 kJ mol–1) and alkanols (2.7 kJ mol–1). No significant isotope effects on Ks are observed when deuterated cyclohexane is complexed with the same cyclodextrins. Similarly, there is no significant effect when deuterated water is used as solvent. Moderate enantioselectivities of up to 2.0 are obtained with some chiral guests.
No preview · Article · Aug 1998 · Journal of the Chemical Society Perkin Transactions 2
[Show abstract][Hide abstract] ABSTRACT: Nine novel cyclodextrin derivatives were synthesized and characterized by H-NMR, C-NMR, FT-IR, TLC, and elemental analysis. A solvent mixture consisting of acctone and water(5:1) was found effective for separation and purification of modified cyclodextrins bearing one or two hydrophobic moieties. The purification method of β-CD—6—OTs was improved.
No preview · Article · Mar 1995 · Synthetic Communications