Discovery and Genetic Characterization of a Vestimentiferan, Lamellibrachia satsuma, from the Submarine Volcano Omuro Dashi in the Izu-Ogasawara Arc.

Vestimentiferan tube worms (Annelida: Siboglinidae) were discovered in a hydrothermal field at a depth of 195 m in the crater of the submarine volcano Omuro Dashi in the Izu-Ogasawara Arc. Based on the nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene in individuals sampled in 2022, they were identified as Lamellibrachia satsuma Miura, Tsukahara & Hashimoto, 1997. STRUCTURE analysis and discriminant analysis of principal components (DAPC) based on 14 microsatellite markers showed a large genetic deviation of the population of Omuro Dashi from those of Kagoshima Bay and the north Mariana Arc (the Nikko and Daikoku Seamounts), whereas the population of Omuro Dashi did not show significant genetic deviation from that of the Nikko Seamount based on the COI gene. All analyses showed that individuals of a methane seep area on the Kanasu-No-Se Bank, the Nankai Trough, which were collected only in 1994, were more closely related to those of Omuro Dashi than to those of other habitats. These results suggest that the ancestors of the Omuro Dashi and Nankai Trough populations originated from migrants from the north Mariana Arc and that there might be undiscovered source population(s) of L. satsuma around the Nankai Trough.

Efficient chemo-enzymatic syntheses of pharmaceutically useful unnatural 2'-deoxynucleosides.

Our chemo-enzymatic method was successfully applied to the synthesis of 2-chloro-2'-deoxyadenosine (CdA, cladribine) in two ways: 1) direct conversion of chemically synthesized 2-deoxy-alpha-D-ribose 1-phosphate (dRP) to CdA; 2) a two-step route via 9-(2-deoxy-beta-D-ribos-1-yl)-2, 6-dichloropurine (Cl2Pu-dR, 5).

Synthesis of 2-deoxy-beta-D-ribose 1-phosphate, NMR comparison and its enzymatic activity for structural elucidation of synthetic alpha-isomer.

2-Deoxy-beta-D-ribose 1-phosphate (1) was synthesized in a stereoselective manner and isolated with no detectable contamination by its alpha-isomer (4). Explicit configuration of 4 was first determined by NMR comparison with 1 judging from NOE results and their coupling constants. Natural purine nucleoside phosphorylase (PNPase) did not recognize 1 and gave no products such as alpha- or beta-deoxynucleosides.

A new approach for syntheses of 2',3'-dideoxy-2',3'-dehydronucleosides using 2,2-difluoro-1,3-dimethylimidazolidine (DFI) as a dehydrating reagent.

We found that 2,2-difluoro-1,3-dimethylimidazolidine (DFI) is useful for not only fluorination but also dehydrating reactions. This dehydrating ability of DFI was applied to the syntheses of dihydrofurans (2) that are possible starting materials for various anticancer or antiviral drugs.

Development of new amination reaction at 4-position of pyrimidine nucleosides.

A new method for the syntheses of the 4-amino-pyrimidine nucleosides (1a, b) has been developed. The method consists of conversion of uridines into quaternary-ammonium intermediates (4a, b) by the reaction with p-toluenesulfonyl chloride(TsCl) in the presence of tertiary-amines, followed by amination with aq NH3. The method is expedient for large-scale preparation of cytidines like 2'-deoxycytidine (1a) or 2'-deoxy-5-methylcytidine (1b).

First stereoselective synthesis of 2-deoxy-alpha-D-ribosyl-1-phosphate: novel application of crystallization-induced asymmetric transformation.

A first stereoselective synthesis of bis(cyclohexylamine) 2-deoxy-alpha-D-ribosyl-1-phosphate has been achieved. The synthesis features a key crystallization-induced asymmetric transformation (AT) to generate a desired alpha-anomer in 99% yield at a 98.8:1.2 ratio of alpha/beta.

Chemo-enzymatic syntheses of natural and unnatural 2'-deoxynucleosides.

A chemo-enzymatic method for preparations of natural and unnatural deoxynucleosides was developed. The method consists of chemical synthesis of natural and unnatural deoxyribose 1-phosphates and their enzymatic conversion to deoxynucleosides. A highly stereoselective synthesis of 2-deoxyribose 1-phosphate was first achieved by an unprecedented application of crystallization-induced asymmetric transformation. Additionally, we first discovered a 2'-deoxycytidine producing enzyme. The discovery and the development of a scalable synthetic process of 2-deoxyribose 1-phosphate enabled us to manufacture all four natural 2'-deoxynucleosides practically. The methodology was applied to the synthesis of 2',3'-dideoxy-3'-fluoroguanosine via synthetic 2,3-dideoxy-3-fluororibose 1-phosphate.