ABSTRACT
Enantioselective total synthesis of the aglycone of burnettramic acid A, an antifungal pyrrolizidinedione with a terminally mannosylated long acyl chain produced by Aspergillus fungi, has been achieved from a known carboxylic acid by a 14-step sequence. The key steps include 2 types of asymmetric alkylation, coupling of an acetylide intermediate with (S)-epichlorohydrin to provide an acetylenic epoxide in 1 pot, and the Birch reduction to effect desulfonylation, semi-reduction of triple bond, and debenzylation in a concurrent manner. Good agreement of the synthetic aglycone with naturally occurring one in 1H and 13C nuclear magnetic resonance (NMR) spectra, coupled with previously reported unambiguous stereochemical assignment of the sugar moiety, has confirmed the structure of burnettramic acid A.
Subject(s)
Stereoisomerism , AlkylationABSTRACT
A diastereo- and enantioselective total synthesis of diocollettines A with an unusual oxygen-containing tricyclic ring system has been achieved in 63% overall yield from commercially available 3-phenylpropanal via four steps. The key feature of the present synthesis is an exclusively diastereoselective cascade sequence composed of a trans-selective oxa-Michael addition of 1,3-dihydroxyacetone to a 2,3-dihydropyrylium ion intermediate, intramolecular aldol-type reaction, and intramolecular acetalization.
ABSTRACT
In the design of the orally disintegrating films (ODFs), it is important to determine the disintegration time (DT) precisely and properly. These films' DTs are usually assessed by a disintegration test defined in the pharmacopoeias, but under the conditions of such tests, a much larger volume of water is used and a stronger up-down movement is applied compared to the conditions of the human oral cavity. Here we developed and tested our new disintegration test system for ODFs. We chose a disintegration test device (the Tricorptester®, Okada Seiko, Tokyo) for orally disintegrating tablets. This device enabled the mechanical dropping of the test medium. We designed an exclusive fixture for ODFs, made an opening in the center of the fixture, and optimized the size of the opening (i.e., the cell). We also investigated that test conditions including the types of test media, the dropping height, flow rate, dropping methods, and medium holding methods. With a passage sensor attached to the Tricorptester, the device was able to automatically detect the DTs of ODFs. We thus successfully developed a new disintegration test system and optimized the operating conditions. Using this system, model ODFs and the commercial ODFs can be properly evaluated.
