1.Synthesis of fused heteroarylprolines and pyrrolopyrroles.
Jeannotte G1, Lubell WD. J Org Chem. 2004 Jul 9;69(14):4656-62.
Fused heteroarylprolines were prepared starting from 4-oxo-N-(PhF)proline benzyl ester (6, PhF = 9-(9-phenylfluorenyl)) following two approaches. First, allylation of oxoproline 6 followed by Wacker oxidation gave 1,4-dione 8 that was selectively converted to pyrroloproline 10b, pyrrolopyrrole 12, and pyridazinoproline 9. Second, aldol condensation of oxoproline 6 with a series of N-(Boc)-alpha-amino aldehydes 15a-e and acid-catalyzed cyclization gave pyrroloprolines 17a-e possessing a variety of pyrrole 5-position substituents. Conditions for the selective deprotection and alkylation of the pyrrole nitrogen of pyrroloprolines 17 were developed to expand the diversity of the heteoaryl systems. Finally, hydrogenolytic cleavage of the PhF and benzyl groups followed by subsequent protection with Boc, Fmoc, and Moz groups was performed to obtain analogues suitable for peptide synthesis. The enantiomeric purity of N-(Boc)pyrrolo-proline 21a was ascertained by coupling to l- and d-phenylalanine methyl ester and examination of the diastereotopic pyrrole protons, which demonstrated the dipeptides to be of >99% diastereomeric purity.
2.Synthesis of sulfonamides and evaluation of their histone deacetylase (HDAC) activity.
Oh S1, Moon HI, Son IH, Jung JC, Avery MA. Molecules. 2007 May 24;12(5):1125-35.
A simple synthesis of sulfonamides 4-22 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involve N-sulfonylation of L-proline benzyl ester hydrochloride (2) and coupling reaction of N-sulfonyl chloride 3 with amines in high yields. It was found that several compounds showed good cellular potency with the most potent compound 20 exhibiting an IC50 = 2.8 microM in vitro.
3.Syntheses of triglycosyl tetrapeptides and a hexaglycosyl tetrapeptide.
Takeda T1, Kanemitsu T, Shimizu N, Ogihara Y, Matsubara M. Carbohydr Res. 1996 Mar 22;283:81-93.
A stereo-controlled synthesis of the model compound for the phytoalexin elicitor-active glycoprotein is described. Glycosylation of the trisaccharide, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl-(1-->6)-2,3,4-tri-O-acetyl- alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl trichloroacetimidate (12), with N-(9-fluorenylmethoxycarbonyl)-L-seryl-L- proline benzyl ester (3) or N-(carbobenzoxy)-L-seryl-L-proline methyl ester (4) by use of BF3. OEt2 gave the triglycosyl-seryl-proline derivatives. The N- as well as C-terminus of these triglycosyl dipeptides could be deblocked selectively to give compounds 14 and 16, which are versatile intermediates for the completion of model compound synthesis of glycopeptide. Triglycosyl tetrapeptides (18, 21) and hexaglycosyl tetrapeptide (23) have been prepared by the convergent block synthesis.
4.Deazapurine solid-phase synthesis: construction of 3-substituted pyrrolo[3,2-d]pyrimidine-6-carboxylates on cross-linked polystyrene bearing a cysteamine linker.
Rombouts FJ1, Fridkin G, Lubell WD. J Comb Chem. 2005 Jul-Aug;7(4):589-98.
The first solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidines is presented. Merrifield resin bearing a cysteamine "traceless" linker was treated with 4-oxo-N-(PhF)proline benzyl ester (10; PhF = 9-(9-phenylfluorenyl)) to provide resin-bound aminopyrrole 20, which was treated with ethyl, phenyl, 4-phenoxyphenyl, and 2,4-dimethoxyphenyl isocyanates to furnish resin-bound ureidopyrroles 21a-d. Resin-bound pyrrolo[3,2-d]pyrimidines 22a-d were then obtained by acylation of 21 using trichloroacetyl chloride in dioxane followed by treatment with Cs2CO3 in DMF. Cleavage of pyrrolo[3,2-d]pyrimidines 22a-d from the resin was achieved in two steps, by oxidation of the sulfur to the sulfone followed by beta-elimination in the presence of t-BuONa. Four pyrrolo[3,2-d]pyrimidines, 24a-d, with different alkyl and aryl substituents at the N3 pyrimidine nitrogen, were thus obtained in overall yields of 42-50% and purities of 90-100%.
