Tomohiko Kawate

Crystallographic and Functional Studies of Very Short Patch Repair Endonuclease

Vsr endonuclease plays a crucial role in the repair of TG mismatched base pairs, which are generated by the spontaneous degradation of methylated cytidines; Vsr recognizes the mismatched base pair and cleaves the phosphate backbone 5 to the thymidine. We have determined the crystal structure of a truncated form of this endonuclease at 1.8 A resolution. The protein contains one structural zinc-binding module. Unexpectedly, its overall topology resembles members of the type II restriction endonuclease family. Subsequent mutational and biochemical analyses showed that certain elements in the catalytic site are also conserved. However, the identification of a critical histidine and evidence of an active site metal-binding coordination that is novel to endonucleases indicate a distinct catalytic mechanism.

Total synthesis of (+)-fumitremorgin B, its epimeric isomers, and demethoxy derivatives

Total synthesis of the title compounds is described. The key intermediate, dehydro-pentacyclic 13, is prepared in a sequence involving Pictet-Spengler reaction and DDQ oxidation. The key step in the synthesis was the dihydroxylation of 13 to afford the cis-diol 54, which was performed by direct oxidation with osmium tetroxide, whereas treatment of 13 with N-bromo-succinimide provided the trans-diol 41. Subsequent selective prenylation of 41 and 54 gave 13-epi-fumitremorgin B (45) and fumitremorgin B (1), respectively. 13-Epi-compound 45 is also converted into fumitremorgin B (1) by oxidation followed by reduction.

Asymmetric reductions of imines and ketones by chiral oxaborolidines

Abstract Asymmetric reduction of imines were studied using dialkoxyborane 1 . Dihydro-β-carboline 5a showed moderate (42%ee) and N -phenylketimine 10 higher enantioselectivity (73%ee). Asymmetric reduction of ketones with oxazaborolidine 33 showed high ennatioselectivities.

Synthetic approach to the total synthesis of fumitremorgins II synthesis of optically active pentacyclic intermediates and their dehydrogenation

Abstract Optically active pentacycles ( 13–18 ) were synthesized from L- and D-tryptophans, two of which ( 13 and 15 ) were alkylated and dehydrogenated to 21 and 22 , respectively.

A synthesis of so-called fumitremorgin C

Abstract 12α- and 12β-Fumitremorgin C (1 and 2) were prepared from the N-prolyl-7-methoxy-β-carboline 4, an intermediate to the synthesis of fumitremorgin B.

ENANTIOSELECTIVE ASYMMETRIC PICTET-SPENGLER REACTION CATALYZED BY DIISOPINOCAMPHEYLCHLOROBORANE

Abstract The first example of a reagent-controlled enantioselective Pictet-Spengler reaction is demonstrated. Employing diisopinocampheylchloroborane as a chiral Lewis acid catalyst, the Pictet-Spengler reaction of N b- hydroxytryptamine gave the corresponding 2-hydroxy-tetrahydro-β-carbolines up to 90 %ee.

Asymmetric reduction of imines with chiral dialkoxyboranes

Abstract The asymmetric reduction of imines with chiral dialkoxyboranes was investigated and gave an optically active amine up to 73%ee in the presence of MgBr 2 ·OEt 2 .

Asymmetric Pictet-Spengler reaction with chiral-N-(β-3-indoly)ethyl-1-methylbenzylamine

Abstract A chiral auxiliary mediated Pictet-Spengler reaction of tryptamine and aldehydes provided 1-substituted tetrahydro-β-carbolines (∼72 % de).