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Platinum (Pt) drugs, including cisplatin, are widely used for the treatment of solid tumors. Despite the clinical success, side effects and occurrence of resistance represent major limitations to the use of clinically available Pt drugs. To overcome these problems, a variety of derivatives have been designed and synthetized. Here, we summarize the recent progress in the development of Pt(II) and Pt(IV) complexes with bioactive ligands. The development of Pt(II) and Pt(IV) complexes with targeting molecules, clinically available agents, and other bioactive molecules is an active field of research. Even if none of the reported Pt derivatives has been yet approved for clinical use, many of these compounds exhibit promising anticancer activities with an improved pharmacological profile. Thus, planning hybrid compounds can be considered as a promising approach to improve the available Pt-based anticancer agents and to obtain new molecular tools to deepen the knowledge of cancer progression and drug resistance mechanisms.

Inhaled siRNA therapy has a unique potential for treatment of severe lung diseases, such as cystic fibrosis (CF). Nevertheless, a drug delivery system tackling lung barriers is mandatory to enhance gene silencing efficacy in the airway epithelium. We recently demonstrated that lipid-polymer hybrid nanoparticles (hNPs), comprising a poly(lactic-co-glycolic) acid (PLGA) core and a lipid shell of dipalmitoyl phosphatidylcholine (DPPC), may assist the transport of the nucleic acid cargo through mucus-covered human airway epithelium. To study in depth the potential of hNPs for siRNA delivery to the lungs and to investigate the hypothesized benefit of PEGylation, here, an siRNA pool against the nuclear factor-kappa B (siNF kappa B) was encapsulated inside hNPs, endowed with a non-PEGylated (DPPC) or a PEGylated (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) or DSPE-PEG) lipid shell. Resulting hNPs were tested for their stability profiles and transport properties in artificial CF mucus, mucus collected from CF cells, and sputum samples from a heterogeneous and representative set of CF patients. Initial information on hNP properties governing their interaction with airway mucus was acquired by small-angle X-ray scattering (SAXS) studies in artificial and cellular CF mucus. The diffusion profiles of hNPs through CF sputa suggested a crucial role of lung colonization of the corresponding donor patient, affecting the mucin type and content of the sample. Noteworthy, PEGylation did not boost mucus penetration in complex and sticky samples, such as CF sputa from patients with polymicrobial colonization. In parallel, in vitro cell uptake studies performed on mucus-lined Calu-3 cells grown at the air-liquid interface (ALI) confirmed the improved ability of non-PEGylated hNPs to overcome mucus and cellular lung barriers. Furthermore, effective in vitro NF kappa B gene silencing was achieved in LPS-stimulated 16HBE14o-cells. Overall, the results highlight the potential of non-PEGylated hNPs as carriers for pulmonary delivery of siRNA for local treatment of CF lung disease. Furthermore, this study provides a detailed understanding of how distinct models may provide different information on nanoparticle interaction with the mucus barrier.

The elucidation of the structure of enzymes and their complexes with ligands continues to provide invaluable insights for the development of drugs against many diseases, including bacterial infections. After nearly three decades since the World Health Organization’s (WHO) declaration of tuberculosis (TB) as a global health emergency, Mycobacterium tuberculosis (Mtb) continues to claim millions of lives, remaining among the leading causes of death worldwide. In the last years, several efforts have been devoted to shortening and improving treatment outcomes, and to overcoming the increasing resistance phenomenon. The structural elucidation of enzyme-ligand complexes is fundamental to identify hot-spots, define possible interaction sites, and elaborate strategies to develop optimized molecules with high affinity. This review offers a critical and comprehensive overview of the most recent structural information on traditional and emerging mycobacterial enzymatic targets. A selection of more than twenty enzymes is here discussed, with a special emphasis on the analysis of their binding sites, the definition of the structure–activity relationships (SARs) of their inhibitors, and the study of their main intermolecular interactions. This work corroborates the potential of structural studies, substantiating their relevance in future anti-mycobacterial drug discovery and development efforts.

Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the 1H, 13C, and 15N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.

Deubiquitinases (DUBs) mediate the removal of ubiquitin from diverse proteins that participate in the regulation of cell survival, DNA damage repair, apoptosis and drug resistance. Previous studies have shown an association between activation of cell survival pathways and platinum-drug resistance in ovarian carcinoma cell lines. Among the strategies available to inhibit DUBs, curcumin derivatives appear promising, thus we hypothesized their use to enhance the efficacy of cisplatin in ovarian carcinoma preclinical models. The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays. When CAPE was combined with cisplatin in nine cell lines representative of various histotypes a synergistic effect was observed in TOV112D cells and in the cisplatin-resistant IGROV-1/Pt1 variant, both of endometrioid type and carrying mutant TP53. In the latter cells, persistent G1 accumulation upon combined treatment associated with p27

Self-synthesizing materials, in which supramolecular structuring enhances the formation of new molecules that participate to the process, represent an intriguing notion to account for the first appearance of biomolecules in an abiotic Earth. We present here a study of the abiotic formation of interchain phosphodiester bonds in solutions of short RNA oligomers in various states of supramolecular arrangement and their reaction kinetics. We found a spectrum of conditions in which RNA oligomers self-assemble and phase separate into highly concentrated ordered fluid liquid crystal (LC) microdomains. We show that such supramolecular state provides a template guiding their ligation into hundred-bases long chains. The quantitative analysis presented here demonstrates that nucleic acid LC boosts the rate of end-to-end ligation and suppresses the formation of the otherwise dominant cyclic oligomers. These results strengthen the concept of supramolecular ordering as an efficient pathway toward the emergence of the RNA World in the primordial Earth.

The proteins involved in the autophagy (Atg) pathway have recently been considered promising targets for the development of new antimalarial drugs. In particular, inhibitors of the protein-protein interaction (PPI) between Atg3 and Atg8 of Plasmodium falciparum retarded the blood- and liver-stages of parasite growth. In this paper, we used computational techniques to design a new class of peptidomimetics mimicking the Atg3 interaction motif, which were then synthesized by click-chemistry. Surface plasmon resonance has been employed to measure the ability of these compounds to inhibit the Atg3-Atg8 reciprocal protein-protein interaction. Moreover, P. falciparum growth inhibition in red blood cell cultures was evaluated as well as the cyto-toxicity of the compounds.

Summary The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer’s patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help., Graphical Abstract, Highlights • P2X7 receptor activity in Tfh cells is important for shaping the gut microbiota • Control of secretory IgA by Tfh cells promotes a healthy gut ecosystem • Lack of P2X7 in Tfh cells results in selection of an obesogenic microbiota • Sensing of extracellular ATP by P2X7 in Tfh cells promotes host metabolic balance, Gut commensals contribute to host metabolic homeostasis. ATP released by bacteria limits IgA secretion in the small intestine via the P2X7 receptor expressed in T follicular helper cells. Perruzza et al. show that this regulatory mechanism is important for shaping a diverse microbiota that promote host metabolic homeostasis.

A cinética de adsorção dos compostos BTX (benzeno, tolueno, o-xileno) em solução aquosa foi investigada em um reator em batelada a 23 ±1°C usando carvão de casca de coco ativado termicamente comercial, como adsorvente. O pH da solução não afetou a adsorção e a ativação térmica do adsorvente produziu uma maior quantidade de cargas negativas na superfície, aumentando a eficiência de adsorção, devido às cargas das moléculas dos BTX serem fracamente positivas. Para determinar o mecanismo e a etapa limitante do processo de adsorção, os dados cinéticos foram ajustados usando diferentes modelos: modelos de pseudo-primeira ordem, pseudo-segunda ordem e difusão intrapartícula. O modelo de pseudo-segunda ordem foi o mais apropriado para descrever a taxa de adsorção com base no alto coeficiente de correlação (R2) e porque o qe calculado utilizando o modelo de pseudo-segunda ordem foi razoavelmente semelhante aos valores experimentais. Através de um estudo detalhado envolvendo os experimentos cinéticos, também foi possível identificar o estágio controlador do processo a partir do ajuste do modelo de difusão intrapartícula. Os valores elevados para os coeficientes de correlação indicaram que o processo é fortemente controlado pelo segundo estágio da difusão para todos os compostos estudados em diferentes concentrações.

Signal transducer and activator of transcription 3 (STAT3) is a validated anticancer target due to the relationship between its constitutive activation and malignant tumors. Through a virtual screening approach on the STAT3-SH2 domain, 5,6-dimethyl-1H,3H-2,1,3-benzothiadiazole-2,2-dioxide (1) was identified as a potential STAT3 inhibitor. Some benzothiadiazole derivatives were synthesized by employing a versatile methodology, and they were tested by an AlphaScreen-based assay. Among them, benzosulfamide 1 showed a significant activity with an IC50 = 15.8 &plusmn, 0.6 &micro, M as a direct STAT3 inhibitor. Notably, we discovered that compound 1 was also able to interact with cysteine residues located around the SH2 domain. By applying mass spectrometry, liquid chromatography, NMR, and UV spectroscopy, an in-depth investigation was carried out, shedding light on its intriguing and unexpected mechanism of interaction.

New glucuronosyldiacylglycerol (GlcADG) analogues based on a 2-O-β-d-glucopyranosyl-sn-glycerol scaffold and carrying one or two acyl chains of different lengths have been synthesized as phosphatidylinositol 3-phosphate (PI3P) mimics targeting the protein kinase Akt. The Akt inhibitory effect of the prepared compounds was assayed using an in vitro kinase assay. The antiproliferative activity of the compounds was tested in the human ovarian carcinoma IGROV-1 cell line in which we found that two of them could inhibit proliferation, in keeping with the target inhibitory effect.

We generalize Pearl's back-door criterion for directed acyclic graphs (DAGs) to more general types of graphs that describe Markov equivalence classes of DAGs and/or allow for arbitrarily many hidden variables. We also give easily checkable necessary and sufficient graphical criteria for the existence of a set of variables that satisfies our generalized back-door criterion, when considering a single intervention and a single outcome variable. Moreover, if such a set exists, we provide an explicit set that fulfills the criterion. We illustrate the results in several examples. R-code is available in the R-package pcalg., Published at http://dx.doi.org/10.1214/14-AOS1295 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction power, whereas the diazabicyclononane was less effective. Biological data were rationalized through a computational study that allowed the conformational preferences of the compounds to be determined and a correlation between the inhibitory activity, the bridge length of the bicycle, and the rotational barrier around dihedral angle τ7 to be hypothesized. A high-field NMR analysis supported the modeling results.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Química, Florianópolis, 2017. Grandes volumes de gás natural (GN) são emitidos ou queimados em plataformas de petróleo, liberando metano, monóxido de carbono e, majoritariamente, dióxido de carbono. Estes gases são responsáveis pelo efeito estufa e representam um sério risco ao meio ambiente e à saúde das pessoas que estão nas proximidades dos locais de emissão, devido a sua toxicidade. Composto predominantemente por metano, o GN é uma fonte de energia segura e possui baixos teores de contaminantes, sendo considerado o combustível fóssil mais limpo. Devido à grande distância entre os reservatórios e os centros consumidores, a construção de gasodutos é economicamente inviável. Em contrapartida, o metano pode ser convertido em combustíveis líquidos através de tecnologias Gas-to- Liquids. A primeira etapa desses processos é a conversão do metano em gás de síntese, que pode ser realizada por diferentes métodos. Dentre os possíveis métodos, a tecnologia de oxidação parcial catalítica do metano (OPCM) oferece diversas vantagens, como menor tempo de residência, menores temperaturas de operação e razão H2/CO ótima para o processo subsequente de Fischer-Tropsch. No presente trabalho foram sintetizados três catalisadores suportados em malhas oxidadas de liga FeCrAl (FCO): FCO/5%Ce, FCO/5%Ce/1%Pt e FCO/0,9%Pt/0,1%Rh, os quais foram caracterizados por difração de raios X (DRX), análise BET, microscopia eletrônica de varredura (MEV) e espectroscopia de energia dispersiva de raios X (EDS). Os catalisadores foram testados para a produção de gás de síntese através do processo de OPCM. A atividade catalítica do suporte virgem e oxidado também foi analisada. A reação teve início entre 600 °C e 700 °C para todos os catalisadores, a 1 bar. Ensaios realizados a 20 bar evidenciaram que o desempenho dos catalisadores diminui com o aumento da pressão. Para o catalisador que apresentou melhor desempenho catalítico (FCO/0,9%Pt/0,1%Rh) foi realizada uma otimização das condições de reação, variando a temperatura do reator (850 a 950 °C), pressão do sistema (1 e 20 bar) e razão molar O2/CH4 (0,40 a 0,70). O catalisador FCO/0,9%Pt/0,1%Rh sofreu leve desativação ao longo de 255 min sob condições ótimas. Experimentos de OPCM consecutivos mostraram que o catalisador pode ser regenerado com oxigênio, mantendo sua atividade catalítica. Os resultados deste trabalho apontam que o FCO é um excelente suporte e pode oxidar metano parcialmente a baixas e altas pressões. Abstract : A substantial amount of natural gas is vented or burnt in oil platforms, releasing methane, carbon monoxide and, mostly, carbon dioxide into the atmosphere. These components are greenhouse gases and represent a serious risk to the environment and to the health of local people, due to their toxicity. The natural gas is composed mostly of methane, it is a safe source of energy with low impurity content and it is considered the cleanest fossil fuel. Due to the large distance between the reservoirs and customers, the pipelines building are uneconomic. However, methane can be converted to liquid fuels through Gas-to-Liquids technologies. The first step of this process is the conversion of methane into synthesis gas, which can be performed through different routes. Among the possible methods, the catalytic partial oxidation of methane (CPOM) presents some advantages like lower residence time, lower reaction temperatures and optimal H2/CO ratio to the subsequent Fischer- Tropsch process. In the present work, three catalysts supported on oxidized FeCrAlloy (FCO) woven were synthesized: FCO/5%Ce, FCO/5%Ce/1%Pt and FCO/0,9%Pt/0,1%Rh; which were characterized by X-ray diffraction (XRD), BET analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The catalysts were tested to produce synthesis gas through the CPOM process. The catalytic activity of the virgin and oxidized support was analyzed. The reaction began between 600 °C and 700 °C for all catalysts, at 1 bar. Experiments performed at 20 bar pointed that the catalyst performance decreased at higher pressures. The reaction conditions were optimized for the catalyst that showed the best performance (FCO/0,9%Pt/0,1%Rh), varying the reactor temperature (850 to 950 °C), system pressure (1 and 20 bar) and the O2/CH4 molar ratio (0,40 to 0,70). The FCO/0,9%Pt/0,1%Rh catalyst has been slightly deactivated over 255 min under optimal conditions. Successive experiments of CPOM indicate that the catalysts can be regenerated with oxygen, maintaining their catalytic activity. The results of this work indicate that the FCO is an excellent support and it can oxidize methane partially at low and high pressures.

New sulfoquinovose analogues of phosphatidylinositol 3-phosphate have been synthesised based on a sulfoquinovose scaffold as potential protein kinase B (PKB) inhibitors. The synthetic strategy involved the introduction into glucose of a thioacetate group at the 6-position and of an azide group at the anomeric position as precursors of the sulfonate and phosphoramidate moieties present in the final compounds. The synthesised compounds were tested in vitro on isolated PKB by means of ELISA assays and for their anti-proliferative activity against the human ovarian carcinoma cell line IGROV-1. Sulfoquinovose derivatives 2b and 2c showed inhibitory activity in the low micromolar range.

Cortexolone-17α-propionate is a topical antiandrogen under investigation for the treatment of androgen-related skin disorders. A full conformational characterization was realized, in comparison with other steroidal androgens and antiandrogens, by means of theoretical calculations at the B3LYP/6-31G(d) level supported by high-field NMR analyses. All of the studied molecules showed a good overlay; nevertheless, the different functional groups present in the skeleton of the molecules drive the individual biological profile.

Signal Transducer and Activator of Transcription 3 (STAT3) is a cytoplasmic factor that mediates intracellular signaling commonly generated at cell surface receptors and transmits it to the nucleus. In previous research studies we synthesized several molecules inhibiting STAT3 and among them oxadiazole MD77 and pyridazinone I showed an interesting activity. For the first one, a direct inhibition mechanism was determined, while I interfered within the STAT3 pathway at a different level. In order to discover novel compounds possibly endowed with an improved activity, we decided to merge their scaffolds on the basis of their calculated conformational properties. Therefore we designed and synthesized the chimera diastereomers 3-oxo-N-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydrobenzo[h]cinnoline-6-carboxamide (1, 2) and 3-oxo-N-(4-(trifluoromethyl)phenyl)-2,3,5,6-tetrahydrobenzo[h]cinnoline-6-carboxamide (3) as racemate and their enantiomeric separation was performed. Modeling studies and theoretical prediction of [α]D values were carried out beside NMR studies which allowed us to assign 1 and 2 relative configurations.

Multi-targeting drug discovery research has been driven, medically, commercially and intellectually; this need has often been equated with the identification and exploitation of novel targets. Glycolipids present both potentials and problems, their biological relevance has been recognized, but problems in procuring lipids rendered them a difficult class of compounds to handle in drug discovery efforts. Sulfoquinovosylacylglycerols (SQAGs), which are one of the abundant sulfur-containing glycerolipids in the biotic world, isolated from different phototrophic organisms, particularly plants and algae, have already been identified as bioactive compounds. In addition to their antiviral activity, their influence on the immune response in mammalian cells is the focus of many studies shown to have an important role in several biological activities. The purpose of this contest is to spotlight the longtime untouched topics of availability, historical background synthesis and recent findings of SQAG's as mammalian DNA polymerase inhibitor, antiangiogenesis, radiosensitizer, immunosuppressive quality, HIV-reverse transcriptase inhibitor, not only for optimizing the treatment of cancer but also for developing the therapeutic approaches for various diseases. This is definitely the beginning of the revolution in the biotic world.

The serine-threonine protein kinase Akt, also known as protein kinase B, is a key component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis. Deregulated activation of this pathway is frequent in human tumors and Akt-dependent signaling appears to be critical in cell survival. PI3K activation generates 3-phosphorylated phosphatidylinositols that bind Akt pleckstrin homology (PH) domain. The blockage of Akt PH domain/phosphoinositides interaction represents a promising approach to interfere with the oncogenic potential of over-activated Akt. In the present study, phosphatidyl inositol mimics based on a β-glucoside scaffold have been synthesized as Akt inhibitors. The compounds possessed one or two lipophilic moieties of different length at the anomeric position of glucose, and an acidic or basic group at C-6. Docking studies, ELISA Akt inhibition assays, and cellular assays on different cell models highlighted 1-O-octadecanoyl-2-O-β-d-sulfoquinovopyranosyl-sn-glycerol as the best Akt inhibitor among the synthesized compounds, which could be considered as a lead for further optimization in the design of Akt inhibitors.

The pcalg package for R can be used for the following two purposes: Causal structure learning and estimation of causal effects from observational data. In this document, we give a brief overview of the methodology, and demonstrate the package’s functionality in both toy examples and applications., Journal of Statistical Software, 47 (11), ISSN:1548-7660

Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.

The first synthesis of the sulfonate analogue of seminolipid, the main sulfoglycolipid in mammalian sperm, is reported. Installation of the sulfonate unit was accomplished by a quite unexplored strategy based on Horner-Wadsworth-Emmons olefination on a 3 '-keto-galactoside, followed by stereoselective double bond reduction.

A convenient chemoenzymatic synthesis of a new class of non-natural sulfo-glycolipids – 2-O-(β-D-sulfoquinovosyl)-monoacylglycerols (2-O-β-D-SQMG) – derived from 2-O-(β-D-glucopyranosyl)glycerol and carrying acyl chains ofvarious lengths at the 1-position of the sn-glycerol moiety, was performed with the aid of a key step involving regioselective lipase-catalyzed acylation of 2-O-(6-deoxy-6-tosyl-β-D-glucopyranosyl)-sn-glycerol (4) at its 1-position, reported here for the first time. Elaboration of the sugar moiety through thioacetate substitution of the selectively inserted tosyl group with subsequent Oxone® oxidation in the presence of unprotected primary and secondary hydroxy groups efficiently afforded the target compounds, the hexanoyl, dodecanoyl, and octadecanoyl derivatives 1a–c, which were active when tested in the EBV-EA in vitro assay for antitumor promoters. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

New sulfoquinovosyldiacylglycerols derived from 2-O-beta-d-glucopyranosyl-sn-glycerol, carrying acyl chains of various length on the glycerol moiety, were prepared through a convenient synthetic procedure in which a sulfonate is introduced at the C-6 position of glucose by oxidation of a thioacetate in the presence of the unprotected secondary hydroxyl groups, and tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation. Our study has allowed to ascertain the role of the 6'-sulfonate group and the need of a free hydroxyl group on the glycerol moiety in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).

The preparation of pimecrolimus, a synthetic derivative of ascomycin endowed with immunomodulatory activity, requires the selective protection of 24-hydroxy group of the ascomycin, before elaboration of the 32-hydroxy group. The aim was achieved by means of two regioselective Candida antarctica lipase-catalyzed steps. The structure of the new key intermediates, 24-, 32-monoacetates, and 24,32-diacetate, was established by means of an unambiguous NMR study.