Succinct Syntheses of Methopholine, (±)‐Homolaudanosine, and (±)‐Dysoxyline via Metal‐free One‐Pot Double Alkylation on 1‐Methyl‐3,4‐dihydroisoquinolines

Abstract

A mild one-pot and metal-free condition was discovered to implement two different alkyl groups chemoselectively on 1-methyl-3,4-dihydroisoquinoline (1-Me-DHIQ), one at the nitrogen another at the C1-methyl group. This chemistry is compatible with various DHIQs as well as alkyl halides. Application of this chemistry facilitated the concise syntheses of methopholine, (AE)-homolaudanosine, and (AE)-dysoxyline, requiring only two steps from 6,7-dimethoxy-1-Me-DHIQ.

Discovery of harmalanium halides as anti‐ovarian cancer agents

“…The counter anions of 3a–f and 4a – f could be unambiguously confirmed, based on the EDS data of 3b and 4d and our previous report (Supporting Information). 7 …”

“…However, typical isolation yields of 5a – f were as low as 20%–40%. Instead of acetonitrile, the choice of ethanol 7 as solvent improved yields to deliver the desired products in 44%–76% yields (Scheme 2).…”

“…The counter anions of 3a-f and 4a-f could be unambiguously confirmed, based on the EDS data of 3b and 4d and our previous report (Supporting Information). 7 With the total of 14 HA analogs prepared in hand, we used A2780 cell lines and cisplatin as control to evaluate anti-ovarian cancer activities (Figure 3). The activity assay was performed at a single concentration of 20 μM for 72 h. While cisplatin exhibited 78% inhibition of A2780 cells, reasonable values considering literature data, 6b it turned out that harmalane (1) and 2-methy harmalanium iodide (2) were not significantly active, inhibiting only 35% and 29%, respectively.…”

“…Recently, we reported a concise method to generate dihydroisoquinolinium halides ( b ) by incorporating two alkyl groups at the C1‐methyl and the nitrogen of 1‐methyl‐3,4‐dihydroisoquinoline ( a ), eventually applying to the synthesis of methopholine, (±)‐homolaudanosine, and (±)‐dysoxyline (Figure 2). 7 With a view to application of this chemistry to the preparation of relatively unexplored HA analogs, we utilized harmalane ( 1 ) 8 to implement the double alkylation chemistry to afford 1,2‐disubstituted harmalanium halides ( 2 – 5 ) and investigated anticancer activities of those compounds in three human ovarian carcinoma cells, including SKOV3, A2780, and cisplatin‐resistant A2780 (A2780‐cis).…”

Biomimetic Total Synthesis of Dysoxylum Alkaloids

“…( S )-Homolaudanosine was the first synthesized derivative of this family (1987), and although several elegant works have been reported during the last 9 years for the total synthesis of Dysoxylum alkaloids, none of them attempted to mimic their biosynthesis, so these approaches involved many synthetic steps, were directed to obtain one or a few compounds, and resulted in poor overall yields (Table ). − …”