Showing papers by "Min Xu published in 2010"

Steroidal Saponins from Fresh Stems of Dracaena angustifolia

Abstract: Six new steroidal saponins (1-6), angudracanosides A-F, were isolated from fresh stems of Dracaena angustifolia, together with eight known compounds. The structures of compounds 1-6 were determined by detailed spectroscopic analyses and chemical methods. Antifungal testing of all compounds showed that 6 and 7 were active against Cryptococcus neoformans with IC(50)s of 9.5 and 20.0 μg/mL, respectively.

Phenolic Antioxidants from the Leaves of Camellia pachyandra Hu.

Abstract: Camellia pachyandra Hu. is a species in Camellia sect. Heterogenea (Theaceae), whose leaves have been used for making tea and consumed by the local people living in Yunnan province, China. This is the first investigation of the chemical constituents in the leaves of C. pachyandra, from which 22 phenolic compounds including nine hydrolyzable tannins (1-9), 11 flavonol glycosides (10-20), and two simple phenolics (21, 22) were isolated. It was noted that the leaves of the title plant contained no caffeine and no catechin, whereas hydrolyzable tannins were found to be the major constituents, of which the content of ellagitannin 5 reached to 3.7%. All the isolates were evaluated for their antioxidant activities by DPPH radical scavenging and tyrosinase inhibitory assays. Though the secondary metabolites without caffeine and catechins are different from the commonly consumed tea plants, the results suggested that the leaves of C. pachyandra, rich in hydrolyzable tannins as potent antioxidants, could be developed as an ideal resource for a natural beverage without caffeine.

Conformationally Constrained Spiro C-Arylglucosides as Potent and Selective Renal Sodium-Dependent Glucose Co-transporter 2 (SGLT2) Inhibitors

Abstract: Diabetes is a highly prevalent modern disease with over 246 million people afflicted worldwide in 2007. A failure of glycemic homeostasis secondary to nutritional imbalance is considered to be the principle explanation for the alarming and increasing incidence of type 2 diabetes mellitus (DM2) in both developed and developing countries. Although a large number of antihyperglycemic agents have been developed to treat the disease, 63 % of DM2 patients fail to achieve the target levels of glycosylated hemoglobin (HbA1C<7 %) recommended by the American Diabetes Association, 4] and consequently these individuals are at risk of developing complications, such as accelerated cardiovascular disease, diabetic nephropathy, retinopathy and ulceration. Recently, renewed emphasis on the development of safe oral antidiabetic agents with a favorable cardiovascular profile has highlighted the attractions of inhibition of renal glucose resorption as a therapeutic mechanism. Sodium glucose co-transporter 2 (SGLT2) is a 672-amino acid, high-capacity, low-affinity transporter expressed nearly exclusively in the S1 and S2 segments of the renal proximal tubule and believed to mediate the majority of renal glucose resorption from the glomerular filtrate. Because the etiology of type 2 diabetes mellitus (DM2) depends on a hypertrophic adipose reservoir, mechanisms that promote glucose disposal by urinary output are therapeutically attractive compared to mechanisms that promote increased glucose assimilation by adipocytes. Selective inhibitors of SGLT2 are expected to be safe because individuals homozygous or compound heterozygous for mutations in SLC5A2, the gene encoding SGLT2, exhibit no significant morbidities. In contrast, penetrant alleles leading to SGLT1 deficiency are the genetic cause of glucose– galactose malabsorption syndrome, which is associated with severe neonatal diarrhea and failure to thrive. In particular, the high selectivity could potentially reduce the gastrointestinal side effect. Hence inhibitors selective for SGLT2 over SGLT1 are attractive candidates for development. Following the initial disclosure of T-1095A, a selective and potent SGLT2 inhibitor designed based on the naturally occurring inhibitor phlorizin, by Tanabe Seiyaku Co., Ltd. (Osaka, Japan), multiple classes of SGLT2 inhibitors have been reported, including Oand C-glucosides. The most advanced inhibitors currently undergoing clinical development in phase III trials, dapagliflozin (1) 16] and canagliflozin, are C-arylglucosides. The studies described here were directed at identifying metabolically robust agents with high selectivity towards SGLT2. Information gained from modeling studies and analysis of the crystal structure of dapagliflozin (1) suggested the possibility of creating novel and conformationally constrained chemotypes with improved potency for SGLT2 by cyclizing the 1and 6’-positions of the glucose moiety and glucose-proximal phenyl ring (Figure 1). Preliminary studies showed that retention of a chlorine substituent at the 4’-position on the proximal phenyl ring is critical for activity. The synthesis and evaluation of three series of novel analogues, which have a different scaffold than previously reported inhibitors, are described here. The synthesis of spiro[isobenzofuran-1,2’-pyran] analogues 12 a–e was addressed first (Scheme 1). Persilylated gluconolactone 3 was prepared in 89 % yield by the slow addition of trimethylsilyl chloride (TMSCl) to commercially available gluconolactone 2 in the presence of N-methylmorpholine. 21] Benzoic acid 4 was subjected to bromination with N-bromosuccinimide (NBS) followed by esterification to yield aniline 6. Sandmeyer reaction and subsequent oxidation of 7 provided the key electron-deficient tetra-substituted benzene 8. Friedel–Crafts acylation of R substituted benzenes generated the benzophenone 9. Selective reduction of the resulting ketone with triethylsilane and further reduction of the methyl ester gave the corresponding benzyl alcohol 10. Protection of the primary hydroxy group with chloromethyl methyl ether produced bromide 11. Lithium–halogen exchange and subsequent coupling with lactone 3 gave a mixture of lactols, which were converted in situ to the desired spiro[isobenzofuran-1,2’-pyran] derivatives 12 a–e in 40 to 63 % yield after purification by preparative thin layer chromatography (TLC). The synthesis of spiro[indane-1,2’-pyran] glucosides 19 a–e was more challenging than that of O-spiroketal C-arylglucosides analogues (Scheme 2). Benzyl alcohol 13 was oxidized with Dess–Martin reagent and subsequently subjected to [a] B. Lv, B. Xu, Prof. Dr. Y. Chen Chengdu Institute of Organic Chemistry (CIOC) Chinese Academy of Sciences (CAS) No. 16, Southion 2, the first circle road, 610041 Chengdu (P.R. China) Fax: (+ 86) 28-8525-9387 E-mail : 51popo51@163.com chenyw@cioc.ac.cn [b] B. Lv, Dr. Y. Feng, Dr. J. Dong, Dr. M. Xu, B. Xu, W. Zhang, Dr. Z. Sheng, Prof. Dr. Y. Chen Egret Pharma (Shanghai) Company, Ltd. Halei Road 1118, 201203 Shanghai (P.R. China) [c] Dr. A. Welihinda, Prof. Dr. B. Seed Theracos Inc. , 550 Del Rey Avenue, Sunnyvale, CA 94805-3528 (USA) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cmdc.201000051.

New C27 Steroidal Bisdesmosides from the Fresh Stems of Dracaena cambodiana

Abstract: Two new steroidal bisdesmosides, cambodracanosides A and B (1 and 2, resp.), were isolated from the fresh stems of Dracaena cambodiana, together with seven known glycosides. The structures of the new saponins were elucidated oil the basis of detailed spectroscopic analyses, including 1D- and 2D-NMR techniques, and acidic hydrolysis.