Asymmetric construction of six vicinal stereogenic centers on hexahydroxanthones via organocatalytic one-pot reactions.

Inspired by the chemistry and biology of hexahydroxanthones, herein we report an organocatalytic Michael-Michael-Aldol-decarboxylation reaction that provides efficient access to biologically interesting fully substituted hexahydroxanthones bearing six contiguous stereogenic centers from readily accessible materials in acceptable yields (up to 63%) and excellent stereoselectivities (up to 10 : 1 dr and >99% ee). In other words, the reaction efficiently produces three chemical bonds and up to six vicinal stereogenic centers in a one-pot operation. In particular, to our knowledge, this is an asymmetric organocatalytic strategy enabling the first construction of six vicinal stereogenic centers on non-spirocyclic hexahydroxanthone frameworks.

Transition-metal-free cascade benzannulations for synthesizing 2-hydroxybenzophenones.

A set of cascade benzannulations of readily accessible chromone-3-carboxaldehydes and γ-nitroaldehydes for synthesizing biologically relevant 2-hydroxybenzophenones has been developed. The cascade was found to provide a transition-metal-free strategy for synthesizing 2-hydroxybenzophenones in acceptable yields (up to 57%).

[Tapping along meridians on back combined with acupuncture of "Qi Shen Zhen" (Seven acupoints for regulating mind) improves symptoms of post-stroke anxiety disorder patients].

OBJECTIVE: To observe the effect of round magnetic needle tapping along meridians on the back plus acupuncture at "Qi Shen Zhen"（including Shenting ［GV24］, Benshen ［GB13］, Sishenchong ［EX-HN1］）, and Baihui （GV20）, Shenmen （HT7） on gastrointestinal function, daily living activities and anxiety status in post-stroke anxiety disorder (PSAD) patients. METHODS: Fifty-seven PSAD patients were randomly divided into acupuncture group (28 cases) and medication group (29 cases). On the basis of routine treatment and physical therapy, patients of the acupuncture group were treated by applying round magnetic needle to mildly tapping the second line→the first line of the Bladder Meridian→Jiaji acupoints→Governor Meridian on the back from outside to the inside in sequence for 20 min, followed by needling GV24, GV20, GB13, EX-HN1 and HT7, respectively, with the needles retained for 30 min after one minute's twisting. The treatment was conducted once daily, 5 times a week, for 6 weeks. Patients of the medication group were asked to take Escitalopram Oxalate tablets (5-20 mg/d) for 6 weeks. The Hamilton Anxiety Rating Scale (HAMA) was used to assess the patient's severity of anxiety, cognition, somatic sensation, symptoms of cardiovascular, respiratory, gastrointestinal, urogenital, automatic and muscular systems, the Barthel Index (BI) used to evaluated the activities of daily living (ADL), and the gastrointestinal function （Spleen-stomach Symptom Score ［SSS］） assessed according to the "Standards for Diagnosis and Curative Effect Evaluation of Syndromes of Traditional Chinese Medicine". The adverse reactions were observed at the end of treatment. RESULTS: After the treatment, the HAMA scores at the 2nd, 4th and 6th week and the SSS scores at the 4th and 6th week were significantly decreased (P<0.05), and the BI scores at the 2nd， 4th and 6th week were considerably increased in both acupuncture and medication groups compared with their own pre-treatment (P<0.05). The HAMA score at the 2nd week, and the SSS scores at the 2nd, 4th and 6th week were obviously lower(P<0.05), and the BI score at the 6th week was notably higher in the acupuncture group than in the medication group (P<0.05). No significant diffe-rence was found between the two groups in the therapeutic effect of anxiety state (P>0.05). The acupuncture group had fewer adverse reactions than the medication group (P<0.05). CONCLUSION: The round magnetic needle tapping plus "Qi Shen Zhen" needling has a significant therapeutic effect in improving PSAD patients' anxiety state, being similar to Escitalopram Oxalate tablets in reducing anxiety state and being superior to Escitalopram in improving gastrointestinal function and daily living activities.

Stereocontrolled construction of six vicinal stereogenic centers on a hexahydroxanthone framework through a formal [2+1+3] annulation.

The first example of a bifunctional donor-donor 3C synthon in situ from activated methine (methyleneindolinone and methylenebenzofuranone) with nitromethane through a [2+1] Michael addition, which further directed the following organocascade Michael/Henry cycloaddition reaction in a one-pot operation is developed, serving as a fruitful strategy for facile access to optically active and structurally diverse hexahydroxanthones with up to six contiguous stereocenters, including a quaternary one. A series of diversely functionalized products are smoothly obtained with up to 76% yield, >20 : 1 d.r. and 98% ee from simple and readily available starting materials. In addition, this is the first example of 3-formyl chromone as an acceptor-acceptor 3C building block, and also the first asymmetric catalytic construction of six vicinal stereogenic centers on a hexahydroxanthone scaffold.

An asymmetric iminium ion catalysis-enabled cascade cycloaddition reaction of chromone-oxindole synthons with enals: construction of a spirooxindole-hexahydroxanthone framework.

We report the first asymmetric iminium ion catalysis-enabled cascade cycloaddition reaction of bifunctional chromone-oxindole synthons and α,ß-unsaturated aldehydes. This allowed one quaternary and four tertiary contiguous stereogenic centers to be constructed in a single operation. A range of spirooxindole-hexahydroxanthone molecules are obtained with up to 62% yield, >20 : 1 dr and >99% ee. This reaction has not only provided a new approach for constructing hexahydroxanthone-fused scaffolds by utilizing asymmetric iminium ion catalysis, but also advanced the chemistry of diversity-oriented synthesis based on bifunctional chromone synthons.