An optimised synthesis of SG3376, a non-cleavable antibody-drug conjugate pyrrolobenzodiazepine drug-linker

In recent years, antibody-drug conjugates (ADCs) have been evaluated in a growing number of clinical trials. Preclinical evaluation and the synthetic accessibility of cleavable pyrrolobenzodiazepine drug-linkers, such as talirine and tesirine, have been previously described. This article details how the synthesis of SG3376, a non-cleavable pyrrolobenzodiazepine drug-linker, has been optimised to provide access to late-stage versatile intermediates in a robust and scalable fashion. Of particular importance was the selective deprotection of primary N-Boc in the presence of secondary N-Boc and secondary O-TBS. SG3376 was conjugated to trastuzumab and the resulting ADC was found to have potent cytotoxic activity in a number of HER2-positive cancer cell lines.     

Microwave-assisted N-debenzylation of amides with triflic acid

A new and facile microwave-assisted protocol for the debenzylation of N-benzylamides with triflic acid has been developed. Both secondary and tertiary aliphatic or aromatic amides are obtained in moderate to good yields.     

Tetrahydropyranyl-protected poly( p -hydroxystyrene) containing vinyl ether compound for three-component photopolymers

Poly(p-hydroxystyrene)s (PHSs) partially protected by tetrahydropyranyl (THP), PPT-x, containing 2,2′-bis(4-(2-(vinyloxy)ethoxy)phenyl)propane as a crosslinking agent were used as three-component photopolymers in combination with diphenyliodonium 9,10-dimethoxyanthracene-2-sulfonate (DIAS) as a photoacid generator. The PPT-x with a higher THP-protecting ratio was deprotected at higher temperatures than the PPT-x with a lower THP-protecting ratio. The conversions of vinyl ether compound in the photopolymer films were not related to the THP-protecting ratios in PPT-x and increased with increasing baking time. Under different THP-protecting ratios and prebaking temperatures, the PPT-x showed varying lithographic behavior between a positive-working mode and a negative-working mode. These three-component photopolymer solutions of PPT-x have good preservation stability. © 1998 John Wiley & Sons, Ltd.     

Deprotection of t-Butyldimethylsiloxy (TBDMS) Protecting Group with Catalytic Copper (II) Chloride Dihydrate

The protection of functional group is unavoidable in multi-step organic synthesis. Alongwith tetrahydropyranyl (THP) ethers, t-butyldimethylsilyl (TBDMS) ethers have beenwidely used for protecting hydroxyl groups. TBDMS ether is more stable to hydrolysisthan trimethylsilyl ether, but is still readily cleaved by a variety of selective conditionsl.The deprotection of TBDMS is usually under mild acidic conditions [AcOH/H,O/THF,3t l: l', or BF, Et,O/CHCI,', etc. '], or with a fluoride…     

Aqueous phosphoric acid as a mild reagent for deprotection of the t-butoxycarbonyl group

Aqueous phosphoric acid (85 wt%) is an efficient and mild reagent for the deprotection of N-BOC groups. Acid sensitive functionalities including benzyl and methyl esters, TBDMS ether, CBZ and isopropylidene groups are compatible with the reaction conditions. The reactions are high yielding, and the workup is convenient.