Hong-Jay Lo

Herein, an enantioselective total synthesis of (−)-panduratin D, a novel secondary metabolite against human pancreatic PANC-1 cancer cell, from commercially available 3-methoxyphenol is reported. The synthesis was completed in nine steps and the key features include Sonogashira coupling, anionic Snieckus–Fries rearrangement, directed ortho metalation, tandem Si → C Alkyl rearrangement/Claisen–Schmidt condensation, and chiral boron complex-promoted asymmetric Diels–Alder cycloaddition. These endeavors could facilitate the biological studies of (−)-panduratin D and its analogs.

The clinically approved Fondaparinux (Arixtra) has been used for the treatment of deep vein thrombosis and acute pulmonary embolism since 2002 and is considered to be better than the low-molecular weight heparin in terms of anticoagulation response, duration of action, and biosafety. However, the synthetic methods previously developed for its manufacture are relatively complicated, thus restricting its extensive use. We report here a potentially scalable and programmable one-pot synthesis of Fondaparinux using the [1,2,2] strategy and designed thioglycosides with well-defined reactivity as building blocks.

A facile and diversity-oriented synthetic strategy toward aminocyclitol natural products from inexpensive C₂-symmetric l-tartaric acid was developed. The pivotal epoxide was used as a common intermediate to accomplish eight diverse target molecules in six to eleven steps. Various allyl-amine-type conduramines were synthesized in a diastereoselective manner. Heck arylation was explored to construct a phenanthridone ring in a concise synthesis of (+)-lycoricidine. In addition, a highly efficient formal synthesis of (−)-laminitol was developed.

Idraparinux is a fully O-sulfated α-methyl glycoside of heparin pentasaccharide motif known to inter-act with the antithrombin III domain and act as anti-coagulant. The current most effective synthesis of Idraparinux is complicated and non-stereoselective, requiring numerous step-wise procedures with low yields. We report here an efficient modular one-pot synthesis of Idraparinux, involving the use of a glycosyl phosphate with 6-O-tert-butyl diphenyl silyl group and a D-glucuronic acid-containing di-saccharide thioglycoside with 6-O-acetyl group as donor building blocks for the α-directing one-pot glycosylations with an L-iduronic acid-containing disaccharide acceptor building block. The uronic acid was incorporated in a disaccharide module used in the one-pot synthesis to avoid the complicated late-stage installation of these acidic sugars. The one-pot synthesis of Idraparinux demonstrated here is an effective strategy and should be applicable to the modular assembly of other heparan sulfates with regiodefined sulfation pattern for functional study.

Fluorinated glycosides are known to resist the glycosidase-catalyzed glycosidic bond cleavage; however the synthesis of such glycans, especially 3-fluoro-sialic acid (3F-Neu5Ac) containing sialosides, has been a major challenge. Though the enzymatic synthesis of α-2,3-linked 3F-sialosides was reported, until recently there has not been any effective method available for the synthesis of 3F-sialosides in the α-2,6-linkage. In order to understand the biological effect of such modification, we report here a chemical synthesis of 3F^ax-Neu5Ac-α2,6-Gal as building block for the assembly of 3F^ax-Neu5Ac-containing sialosides and a representative homogeneous antibody glycoform. Our results showed that the sialosides are stable under sialidase catalysis and the rituximab glycoform with a sialylated complex-type biantennary glycan terminated with 3F^ax-Neu5Ac in the α-2,6-linkage (α2,6-F-SCT) has a similar binding avidity as its parent glycoform. These findings open up new opportunities for the development of therapeutic glycoproteins with improved pharmacokinetic parameters.

Ortho‐hydroxy amides are alkylated by LDA and chlorosilanes.

A chiral pool based synthetic strategy that leads from the readily available and inexpensive C₂-symmetric tartaric acids to the chiral O-isopropylidenebenzooxazole—a convenient precursor to the aminocyclitol core of hygromycin A as well as the chiral γ-disilyloxybutyrolactone—a pivotal intermediate to approach to the furanoside of hygromycin A.

A new enantioconvergent strategy directed toward the synthesis of glucosidase inhibitors was developed by using a C₂‐symmetric element within the chiral pool and by applying an iodine‐promoted cyclization of an unsaturated carbonimidothioate for the regio‐ and diastereocontrolled installation of amino and hydroxy units. Not only does this simple flexible strategy provide a convergent concise approach to (+)‐valiolamine (1), but it can also be readily adopted for the synthesis of (+)‐valienamine (2). Commercially available and cheap C₂‐symmetric D‐tartaric acid served as the chiral building block.