144667-38-9

Upstream product

• 919535-37-8 methyl (S)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1-(chloromethyl)-5-benzyloxy-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 
• 128781-07-7 5,6,7-trimethoxy-1H-indole-2-carboxylic acid 
• 197657-13-9 methyl (1S)-5-benzyloxy-3-t-butoxycarbonyl-1-chloromethyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-7-carboxylate 
• 197657-12-8 methyl (1S)-5-benzyloxy-3-t-butoxycarbonyl-1-hydroxymethyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-7-carboxylate 
• 144786-07-2 methyl (1S)-3-t-butoxycarbonyl-1-chloromethyl-5-hydroxy-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-7-carboxylate 
• 130288-24-3 (+)-duocarmycin SA 
• 144667-37-8 methyl 3-((tert-butyloxy)carbonyl)-1-(chloroxymethyl)-5-hydroxy-1,2-dihydro-3H-pyrrolo<3,2-e>indole-7-carboxylate 
• 144667-36-7 methyl 3-((tert-butyloxy)carbonyl)-5-hydroxy-1-(hydroxymethyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole-7-carboxylate 
• 144667-30-1 O-benzyl-N²,N⁵-dibenzoyl-2,5-diamino-4-(2,2-dimethyl-1,3-dioxan-5-yl)-3-(3,3-dimethoxy-2-oxopropyl)phenol 
• 144667-31-2 N⁵-benzoyl-5-amino-1-benzoyl-7-(benzyloxy)-4-(bis(hydroxymethyl)methyl)-2-(dimethoxymethyl)indole 
• 144667-32-3 5-(benzyloxy)-3,6-dibenzoyl-7-(dimethoxymethyl)-1-(hydroxymethyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole 
• 144667-35-6 methyl 5-(benzyloxy)-3-((tert-butyloxy)carbonyl)-1-(hydroxymethyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole-7-carboxylate 
• 144667-28-7 O-benzyl-N²,N⁵-dibenzoyl-2,5-diamino-4-(2,2-dimethyl-1,3-dioxan-5-yl)phenol 
• 144667-33-4 5-(benzyloxy)-3-((tert-butyloxy)carbonyl)-7-(dimethoxymethyl)-1-(hydroxymethyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole 

Downstream Products

• 130288-24-3 (+)-duocarmycin SA 

Relevant academic research and scientific papers

Systematic exploration of the structural features of yatakemycin impacting DNA alkylation and biological activity

A systematic examination of the impact of the yatakemycin left and right subunits and their substituents is detailed along with a study of its unique three subunit arrangement (sandwiched vs extended and reversed analogues). The examination of the ca. 50 analogues prepared illustrate that within the yatakemycin three subunit structure, the subunit substituents are relatively unimportant and that it is the unique sandwiched arrangement that substantially increases the rate and optimizes the efficiency of its DNA alkylation reaction. This potentiates the cytotoxic activity of yatakemycin and its analogues overcoming limitations typically observed with more traditional compounds in the series (CC-1065, duocarmycins). Moreover, a study of the placement of the alkylation subunit within the three subunit arrangement (sandwiched vs extended and reversed analogues) indicates that it not only has a profound impact on the rate and efficiency of DNA alkylation but also controls and establishes the DNA alkylation selectivity as well, where both enantiomers of such sandwiched agents alkylate the same adenine sites exhibiting the same DNA alkylation selectivity independent of their absolute configuration.

A concise and efficient synthesis of seco-duocarmycin SA

A short and efficient synthesis of seco-duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic

A novel synthesis of (+)-duocarmycin SA

The title synthesis was achieved in eight steps from (S)-5-aminoindoline (S)-4 by a method featuring sequential dehydrogenation, double bond isomerization, and oxidative cyclization of (S)-5-[(1-methoxycarbonylethyl)amino]indoline 5 as the key steps. The sequential reaction was effected by using MnO2-Pd(OAc)2 as the oxidizing agent in the presence of an acid catalyst.

Total synthesis and preliminary evaluation of (+)- and ent-(-)-duocarmycin SA

Concise total syntheses of natural (+)- and ent-(-)-duocarmycin SA (1) are detailed based on sequential regioselective nucleophilic substitution reactions of the unsymmetrical p-quinone diimine 3 in the preparation of a dihydropyrroloindole precursor to the left-hand subunit. In addition to constituting a new synthetic strategy for the preparation of natural or synthetic duocarmycins and related agents, both enantiomers of 2 (N-BOC-DSA) and its immediate synthetic precursors are made available by the approach. This provides access to synthetic analogs incorporating either enantiomer of the exceptionally stable and potent duocarmycin SA alkylation subunit. The comparative chemical properties of the agents are detailed in studies which reveal that N-BOC-DSA (t1/2 = 177 h, pH = 3; stable, pH = 7) is 4.8× more stable to chemical solvolysis than N-BOC-CPI (t1/2 = 37 h, pH = 3), the authentic alkylation subunit of CC-1065, and that the agents participate in a stereoelectronically-controlled solvolysis reaction with nucleophilic addition to the least hindered cyclopropane carbon. Consistent with this enhanced stability, (+)-N-BOC-DSA (2) proved to possess the most potent inherent cytotoxic activity of all natural and synthetic alkylation subunits examined to date including (+)-N-BOC-CPI, and its relative cytotoxic potency predictably follows a fundamental relationship between chemical stability and cytotoxic potency established in prior studies. In contrast to expectations based on past observations, the unnatural enantiomers of 1 and 2 as well as the natural enantiomers were found to constitute potent cytotoxic agents whose further examination should prove exceptionally interesting.