A series of novel OSW-1 analogues were synthesized by coupling disaccharides (2-O-4-methoxylbenzoyl-β-d-xylopyranosyl-(1→3)-2-O-acetyl-α-l-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-β-d-xylopyranosyl-(1→3)-2-O-acetyl-α-l-arabinopyranosyl) and their 1→4 linked analogues [(2-O-4-methoxylbenzoyl-β-d-xylopyranosyl-(1→4)-2-O-acetyl-α-l-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-β-d-xylopyranosyl-(1→4)-2-O-acetyl-α-l-arabinopyranosyl)] with three different steroidal sapogenins at 16β-hydroxy. Their conformation was analyzed with NMR spectroscopy and molecule simulation. The arabinose moiety of 1–3 linked analogues was in chair conformation and 1–4 linked analogues was in boat conformation. 1–3 linked analogues exhibited potent anti-proliferation activity against a panel of human tumor cells at nanomolar concentration level, while 1–4 linked analogues did not show antitumor activity. This work should provide an evidence that the conformation plays an important role in the antitumor activity.The highest antiproliferative activity was displayed by compounds containing 1–3 linked disaccharide which had convergent structures at nanomolar concentrations level. 1–4 linked analogues which had divergent structures showed a lower activity. The key role of triangular molecular shape of 1–3 linked OSW-1 analogues for the high activity was confirmed.

4-Azido modified desosamine 4a was synthesized and coupled to erythronolide 9. Using trichloroacetimidate donor in the presence of TMSOTf was considered as the most efficient condition for the glycosylation reaction. Five novel 14-membered ketolides 12a–e bearing modified 5-O-4′-[1,2,3] triazol desosamine side chain were synthesized by the azide/alkyne click chemistry method.Five novel 14-membered ketolides 12a–e bearing modified 5-O-4′-[1,2,3] triazol desosamine side chain were synthesized.

A series of novel 9-O-acetyl-4′-substituted 16-membered macrolides derived from josamycin has been designed and synthesized by cleavage of the mycarose of josamycin and subsequent modification of the 4′-hydroxyl group. These derivatives were evaluated for their in vitro antibacterial activities against a panel of Staphylococcus aureus and Staphylococcus epidermidis. 15 (4′-O-(3-Phenylpropanoyl)-9-O-acetyl-desmycarosyl josamycin) and 16 (4′-O-butanoyl-9-O-acetyl-desmycarosyl josamycin) exhibited comparable activities to josamycin against S. aureus (MSSA) and S. epidermidis (MSSE).A series of novel 9-O-acetyl-4′-substituted 16-membered macrolides derived from josamycin were synthesized and evaluated for their antibacterial activities.

A series of new 4″-O-desosaminyl clarithromycin derivatives were designed and synthesized. The efficient synthesis routes of 6-deoxy-desosamine donors 8 and 11 were developed and the methodology of glycosylation of clarithromycin 4″-OH with desosamine was studied. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive pathogens, and compounds 19 and 22 displayed significant improvement of activities against sensitive pathogens and two strains of MRSE, which verified the importance of desosamine in the interaction of macrolide and its receptor, and offered valuable information of the SAR of macrolide 4″-OH derivatives.

Four 5,6-dihydro-17-hydroxy icogenin analogs were designed and synthesized. Their in vitro antitumor activities were tested by the standard MTT assay. Compound 22 (IC50 = 3.38–8.30 μM) and compound 23 (IC50 = 1.90–9.69 μM) showed potential antitumor activities against the entire tested seven cancer cell lines. The SAR (structure activity relationship) research showed that the introduction of 17-hydroxy lowered the antitumor activity to an extent.Four 5,6-dihydro-17-hydroxy icogenin analogs were synthesized and tested for antitumor activity.Highlights► We designed and synthesized four 5,6-dihydro-17-hydroxy icogenin analogs. ► 22 (IC50 = 3.38–8.30 μM) and 23 (IC50 = 1.90–9.69 μM) showed potential antitumor activity. ► The introduction of 17-hydroxy lowered the antitumor activity to an extent.

A series of novel modified 5-O-desosamine-ketolides were synthesized. The 5-O-desosamine fragment was removed from ketolide by an efficient and mild manipulation. 4-O-substituted desosamine was introduced into the ketolide aglycon and various coupling methods were essayed for the glycosylation. Three novel ketolides were tested for in vitro antibacterial activity against a panel of susceptible and resistant pathogens. Compound 26 showed potent activity against all the methicillin-sensitivity and resistant pathogens.A series of novel modified 5-O-desosamine-ketolides were synthesized. Three 5-O-glyco-modified ketolides were tested for in vitro antibacterial activity against a panel of susceptible and resistant pathogens.

A novel series of ketolides with 11,12-sulfur contained aryl alkyl side chains were synthesized and evaluated for their antibacterial activity. These ketolides exhibited potent activity against key macrolide sensitive and resistant respiratory pathogens. The newly synthesized 9a, 9e, 9k and 9n showed a similar antimicrobial spectrum and comparable activity to telithromycin, the commercial ketolide antibacterial.A novel series of ketolides with 11,12-sulfur contained aryl alkyl side chains were synthesized and evaluated for their antibacterial activity.Research highlights► Novel ketolides were synthesized and evaluated for their antibacterial activity. ► 9n and 9k showed better antibacterial activity than telithromycin. ► 9a, 9e, 9k and 9n have in vitro antibacterial spectrum similar to telithromycin. ► They are potent against erm and mef-gene containing resistant strains.

To fulfill the structure–activity relationship (SAR) of OSW-1, and aim at finding the simplest structural part while maintaining most of the biological activities, six cholestane saponins were synthesized by introducing OSW-1 disaccharide (2-O-4-methoxybenzoyl-β-d-xylopyranosyl-(1→3)-2-O-acetyl-α-l-arabinopyranosyl) and its 1→4-linked analogue to the 7-hydroxy or 16-hydroxy of steroidal sapogenins. Cytotoxic activities of the products were tested. Compounds 1 and 3 exhibited potent cytotoxicities against five types of human tumor cells, with minimum IC50 of 2.0 and 75 nM, respectively. And due to its high activity and easy accessibility compound 1 could be a potential candidate for new anti-tumor agents.Six cholestane saponins, as mimics of OSW-1, were synthesized and tested for the cytotoxic activities. Compounds 1 and 3 exhibited potent cytotoxicities against five types of human tumor cells, with minimum IC50 of 2.0 and 75 nM, respectively.

In order to study the SAR of 5(6)-dihydro-OSW-1, eight 15(α)β-O-glycosyl analogs (26–33) carrying three kinds of disaccharides including [β-d-Xylp-(1–3)-α-l-Arap], [β-d-Xylp-(1–4)-α-l-Arap] and [α-l-Rhap-(1–2)-(α)β-d-Glcp] were designed and synthesized. Their in vitro antitumor activities were tested by the standard MTT assay which disclosed that compound 33 (IC50 = 0.28–0.52 μM) showed potential antitumor activities.Eight 15(α)β-O-glycosyl 5(6)-dihydro-OSW-1 analogs bearing three kinds of disaccharide side chains were synthesized and evaluated for their antitumor activities.

A series of novel derivatives of macrolide with 4″-O-mono- or disaccharides were synthesized. The corresponding glycosyl trichloroacetimidates were used as the donors in the glycosylations. The in vitro antibacterial activities of 7a–f and 13–16 against a panel of susceptible and resistant pathogens were tested. The modification of 4′′-O-mono- or disaccharides may lead to the understanding of interaction of the macrolide and the bacterial ribosome.A novel series of macrolide derivatives with mono- or disaccharides substituted at the 4′′-O- position has been synthesized, and their in vitro antibacterial activities were tested.

For further structure–activity relationship (SAR) research of OSW saponins, a cholestane glycoside, namely 3β, 16β, 26-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-d-xylopyranosyl)-(1→3)-2-O-acetyl-α-l-arabinopyranoside (1) together with two 1→4-linked disaccharide analogues (2 and 3) were synthesized. Their cytotoxic activities were evaluated by the standard MTT assay. Compound 1 showed potent cytotoxicity against five types of human tumor cells, with IC50 ranging between 1.3 and 73 nM.Three cholestane glycosides bearing the OSW-1 disaccharide or its 1→4-linked analogue were synthesized, and their cytotoxic activities were determined. Compound 1 showed potent cytotoxicity against five types of human tumor cells, with IC50 ranging between 1.3 and 73 nM.

For further structure–activity relationships (SAR) research of furostan saponin, two icogenin analogues: (25R)-22-O-methyl-furost-5-en-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranoside 1 and (25R)-22-O-methyl-furost-5-en-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-α-d-glucopyranoside 2, with valuable disaccharide moieties, were synthesized from diosgenin through eight steps. Both of the analogues behaved the similar cytotoxic activities with icogenin, towards nine types of human tumor cells herein.Two analogues of icogenin with simple disaccharide residues were synthesized in a facile and efficient way. Their cytotoxic activities were studied also.

In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared to telithromycin, compound 15a demonstrated improved in vitro activity against erythromycin-susceptible and -resistant strains.A series of ketolide and acylide derivatives with imidazo[4,5-b] pyridinyl sulfur contained side chains was synthesized. Their in vitro antibacterial activity was evaluated.

A series of novel 4″-position modified macrolide derivatives has been synthesized via a facile procedure. Their in vitro antibacterial activities against constitutively erythromycin-resistant strains were evaluated. Among the derivatives tested, compound 8a which has 11,12-carbamate and 4″-O-heteroarylcarbamoyl groups was found to have potent activity against most resistant bacteria.A series of novel 4′′-position modified macrolide derivatives has been synthesized via a facile procedure. Their antibacterial activities were reported.

A facile and efficient way for the synthesis of cholestane and furostan saponin analogues was established and adopted for the first time. Following this strategy, starting from diosgenin, three novel cholestane saponin analogues: (22S,25R)-3β,22,26-trihydroxy-cholest-5-ene-16-one 22-O-[O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranoside] 11, (25R)-3β,16β,26-trihydroxy-cholest-5-ene-22-one 16-O-[O-α-l-rhamnopyranosyl-(1 → 2)-α-d-glucopyranoside] 14 and (25R)-3β,16β,26-trihydroxy-cholest-5-ene-22-one 16-O-[O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranoside] 17, three novel furostan saponin analogues: (22S,25R)-furost-5-ene-3β,22,26-triol 22-O-(α-d-glucopyranoside) 23, (22R,25R)-furost-5-ene-3β,22,26-triol 22-O-(α-d-glucopyranoside) 24 and (22S,25R)-furost-5-ene-3β,22,26-triol 22-O-[O-α-l-rhamnopyranosyl-(1 → 2)-α-d-glucopyranoside] 26, were synthesized ultimately. The structures of all the synthesized analogues were confirmed by spectroscopic methods. The S-chirality at C-22 of cholestane was confirmed by Mosher's method. The absolute configuration at C-22 of furostan saponin analogues was distinguished by conformational analysis combined with the NMR spectroscopy. The cytotoxicities of the synthetic analogues toward four types of tumor cells were shown also.Research highlights▶ Three cholestane and three furostan saponin analogueswere synthesized in an efficient way. ▶ The absolute configuration of C-22 was determined. ▶ The cytotoxicities of the synthetic analogues were demonstrated also.