First synthesis of the antimalarial naphthylisoquinoline alkaloid dioncophylline C, and its unnatural anti-HIV dimer, jozimine C

The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

“…41,98,[110][111][112] From the resulting dioxytetrahydroisoquinolines (X = OH or OMe), the monooxy analogs (X = H) likewise required can be prepared by reductive deoxygenation. 113,108,2,114 The naphthalene parts (Scheme 28) are prepared either by Stobbe or related reactions of benzaldehydes with subsequent acid-catalyzed ring closure of , 2,115-118 or by Diels-Alder reaction of in situ generated arynes with , 119,120 or by biomimetic cyclization of polyketides built up in a one-step synthesis from diesters and the 'dianion' of acetone. [121][122][123][124] …”

“…An instructive example of this is dioncophylline C (3-), 113 the naphthylisoquinoline alkaloid with the as yet highest antimalarial activity, 14 actually, one can heal malaria-infected mice with dioncophylline C. 130 But there is no oxygen function next to the axis that might serve as a 'bridge head'. Nontheless, dioncophylline C (3-) was synthesized through the lactone methodology (Scheme 36), 114,9 the first and only synthesis of this bioactive natural product: This was achieved by intramolecular coupling of to the highly strained, slowly helimerizing biaryl lactone , again with the option of pushing virtually the whole synthetic material into one atropisomeric form, 0-, by using an 1TFA substituent, followed by ring cleavage to 0-, and then elimination of its oxygen function, which was not required any more now. This ef- .…”

Ligand-free, PdCl2(PPh3)2 catalyzed, microwave-assisted Suzuki coupling of 1-chloro-3-phenylisoquinoline in the synthesis of diversified 1,3-disubstituted isoquinolines

“…1,3-disubstituted isoquinoline skeleton is an integral part of many naturally occurring substances and pharmaceutically important compounds [17][18][19]. 1,3-disubstituted isoquinolines have resulted in them being used as building blocks [20] in pharmaceutical compounds [21], as chiral ligands for the transition metal catalysts [22], and their iridium complexes in organic light-emitting diodes (OLEDs) [23].…”

Facile benzannulation of isocoumarins in the efficient synthesis of diversified 1,3-disubstituted isoquinolines

“…Recently, much attention has been directed towards palladium catalyzed annulations and electrophilic cyclization of alkynes as powerful methods for the construction of various heterocycles, such as isochromenes [3], isoquinolines [4] and benzfurans [5], under mild conditions. The 1,3-disubstituted isoquinolines skeleton forms an integral part of many naturally occurring substances, including pharmaceutically important compounds [6][7][8][9][10], as chiral ligands for the transition metal catalysts [11], and their iridium complexes in organic light-emitting diodes (OLEDs) [12].…”