Development of TfOH-Catalyzed Spirocyclization by Intramolecular Friedel-Crafts-type 1,4-Addition: Application to the Total Synthesis of the Unusual Proaporphine Alkaloid (±)-Misrametine.

An effective method was developed for TfOH-catalyzed construction of spiroindanes and spirotetralines containing an all-carbon quaternary stereocenter. Intramolecular Friedel-Crafts-type 1,4-addition of the substrates which were di- or trimethoxybenzene and 2-cyclohexenone linked by an alkyl chain proceeded smoothly in the presence of 30 mol % of TfOH. A variety of spiroindanes and spirotetralines were obtained with moderate to excellent yield by this method. The reaction was successfully applied in the first total synthesis of the unusual proaporphine alkaloid (±)-misrametine, which included the gram-scale spirocyclization and selective O-demethylation used KCN in DMSO condition as key steps.

Effects of ultra-pure soft water on the hands of nurses in a neonatal intensive care unit: A randomized crossover study.

BACKGROUND: Healthcare workers (HCWs) wash their hands with tap water (TW) and soap. However, hard TW causes dermatitis. OBJECTIVES: The present study aimed to compare the effects of ultra-pure soft water (UPSW) with those of TW on the hands of HWCs. METHODS: The present study was a prospective randomized trial with a crossover design. All the nurses in the neonatal intensive care unit (NICU) at the study centre were divided into Sequence 1 (UPSW to TW) or 2 (TW to UPSW) and washed their hands with TW or UPSW in alternating 4-week periods with a 4-week washout period. Trans-epidermal water loss (TEWL) and stratum corneum hydration (SCH) were evaluated. Skin condition was self-assessed. RESULTS: Twenty-one and 22 nurses were assigned to Sequence 1 and Sequence 2, respectively. USPW increased SCH to a significantly greater degree than TW (mean: 26.3 µS ± 12.3 SD; 95% confidence interval: 1.12-51.54; p = 0.041) although it did not affect TEWL. UPSW use significantly improved the subjects' skin condition, as reflected in an overall increase in the assessment scores. CONCLUSIONS: UPSW improved SCH and the condition of hand skin. Prolonged USPW use may increase nurses' comfort during work and hand hygiene compliance.

Enantioselective Total Synthesis of (-)-Misramine.

The enantioselective total synthesis of an unusual pentacyclic proaporphine alkaloid, (-)-misramine, was achieved. The synthetic strategy relied on an enantioselective intramolecular Friedel-Crafts-type 1,4-addition using an asymmetric organocatalyst to construct a spiroindane skeleton containing an all-carbon quaternary stereocenter and a double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. This work is the first example of asymmetric synthesis of a proaporphine alkaloid.

Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.

The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B.

Total synthesis and conformational analysis of apratoxin C.

Total synthesis of apratoxin C, a cyanobacterial cyclodepsipeptide with highly potent cytotoxicity against some cancer cell lines, was achieved using the apratoxin A synthetic strategy developed by us. To elucidate the relationship between conformation and activity, the tertiary structure of apratoxin C was analyzed by NMR spectroscopy. We obtained 37 ROEs and five (3)JH,H values, which were translated into distance and dihedral angle constraints, respectively. Molecular modeling was performed with a restrained conformational search by a distance geometry method. The lowest energy structure indicated that the methyl group at C37 and the isopropyl group at C39 play critical roles in maintaining the conformation, whereas the methyl group at C34 does not. Moreover, we confirmed that apratoxin A and C possess similar conformations, providing a likely explanation for their nearly equivalent cytotoxicities.

A concise synthesis of 3-aroylflavones via Lewis base 9-azajulolidine-catalyzed tandem acyl transfer-cyclization.

Lewis base-catalyzed tandem acyl transfer-cyclization of acylated o-alkynoylphenols leading to 3-aroylflavones was developed. 9-Azajulolidine smoothly promoted the reaction of the aroyl derivatives at ambient temperature, and the structure-diversed synthesis of 3-aroylflavones with distinct substituents was achieved in moderate to excellent yields.

Synthesis of γ-benzopyranone by TfOH-promoted regioselective cyclization of o-alkynoylphenols.

Regioselective cyclization of o-alkynoylphenols forming γ-benzopyranones has been demonstrated. Trifluoromethanesulfonic acid (TfOH) induced 6-endo cyclization of o-alkynoylphenols without forming 5-exo cyclized benzofuranone derivatives to provide the corresponding γ-benzopyranones in high yields.