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//
// Copyright (C) 2020 Brian P Kelley, Joann Prescott-Roy
//
// @@ All Rights Reserved @@
// This file is part of the RDKit.
// The contents are covered by the terms of the BSD license
// which is included in the file license.txt, found at the root
// of the RDKit source tree.
//
#include "Deprotect.h"
#include <GraphMol/RDKitBase.h>
#include <GraphMol/SmilesParse/SmilesWrite.h>
#include <GraphMol/ChemReactions/ReactionParser.h>
#include <boost/smart_ptr.hpp>
namespace RDKit {
namespace Deprotect {
DeprotectData::DeprotectData(const std::string &deprotection_class,
const std::string &reaction_smarts,
const std::string &abbreviation,
const std::string &full_name,
const std::string &example)
:
deprotection_class(deprotection_class),
reaction_smarts(reaction_smarts),
abbreviation(abbreviation),
full_name(full_name),
example(example),
rxn(RxnSmartsToChemicalReaction(reaction_smarts)) {
if (rxn.get()) {
if (rxn->getNumProductTemplates() != 1) {
BOOST_LOG(rdErrorLog)
<< "Deprotection reactions must have exactly one product"
<< std::endl;
}
rxn->initReactantMatchers();
}
}
const std::vector<DeprotectData> &getDeprotections() {
static const std::vector<DeprotectData> deprotections{
{"alcohol", "CC(C)([Si](C)(C)[O;H0:1])C>>[O;H1:1]", "TBDMS",
"tert-butyldimethylsilyl", "CC(C)(C)[Si](C)(C)OC>>OC"},
{"alcohol", "COc1ccc(C([O;H0:1])(c2ccccc2)c2ccccc2)cc1>>[O;H1:1]", "MMT",
"methoxytrityl",
"COc1ccc(C(ON)(c2ccccc2)c2ccccc2)cc1>>NO"},
{"alcohol", "O1C([O;H0:1])[C;H2][C;H2][C;H2][C;H2]1>>[O;H1:1]", "THP",
"tetrahydropyranyl",
"COC1CCCCO1>>CO"},
{"alcohol", "[C;H3][O;X2&R0][C;H2&R0][O;H0:1]>>[O;H1:1]", "MOM",
"methoxymethyl_ether",
"COCOC>>CO"},
{"alcohol", "[C;R0][O;R0][C;R0][C;R0][O;R0][C;R0][O;X2:1]>>[O;H1:1]",
"MEM", "beta-Methoxyethoxymethyl_ether",
"C(C)(C)OCOCCOC>>C(C)(C)O"},
{"alcohol", "[O;!$(*C(=O)):1]c1[c;H1][c;H1][c;H1][c;H1][c;H1]1>>[O;H1:1]",
"Bn", "benzyl",
"NOc1ccccc1>>ON"},
{"alcohol", "[O;H0&X2:1][Si]([C;H3])([C;H3])([C;H3])>>[O;H1:1]", "TMS",
"trimethylsilyl", "NO[Si](C)(C)C>>NO"},
{"alcohol", "[O;H0:1]C(=O)c1[c;H1][c;H1][c;H1][c;H1][c;H1]1>>[O;H1:1]",
"Bz", "benzoyl", "COC(=O)c1ccccc1>>OC"},
{"alcohol", "[O;H0:1][C;R0](=O)[C;R0]([C;H3])([C;H3])[C;H3]>>[O;H1:1]",
"Piv", "pivaloyl", "CC(C)(C)C(=O)ON>>NO"},
{"alcohol", "[O;H0:1][Si](C(C)C)(C(C)C)(C(C)C)>>[O;H1:1]", "TIPS",
"triisopropylsilyl", "NO[Si](C(C)C)(C(C)C)(C(C)C)>>ON"},
{"alcohol", "[O;R0:1][C;R0](=O)[C;H3]>>[O:1]", "Ac", "acetyl",
"NOC(=O)C>>NO"},
{"alcohol",
"[c;H1]1[c;H1]c(O[C;H3])[c;H1][c;H1]c1[C;H2][O;D2&R0:1]>>[O;H1:1]",
"PMB", "para-methoxybenzyl_ether", "c1cc(OC)ccc1CON>>NO"},
{"alcohol", "c1ccc(C([NX3;H0,H1,H2:1])(c2ccccc2)c2ccccc2)cc1>>[N:1]",
"Tr", "triphenylmethyl", "CN(C)C(c1ccccc1)(c1ccccc1)c1ccccc1>>CNC"},
{"amine", "O=C1[N;H0:1]C(c2[c;H1][c;H1][c;H1][c;H1]c21)=O>>[N:1]", "Phth",
"phthaloyl", "O=C1N(C(=O)c2ccccc12)C1=CC=CC=C1>>Nc1ccccc1"},
{"amine", "[#7:1]COCC[Si]([C;R0])([C;R0])[C;R0]>>[#7:1]", "SEM",
"trimethylsilylethoxymethyl", "C[Si](C)(C)CCOCNO>>NO"},
{"amine",
"[C;H3;R0][O;R0]c1[c;H1][c;H1][c]([NX3;H0,H1;!$(NC=O):1])[c;H1][c;H1]1>>"
"[N:1]",
"PMP", "para-methoxyphenyl", "COc1ccc(NO)cc1>>NO"},
{"amine",
"[C;H3]c1[c;H1][c;H1]c(S(=O)(=O)[NX3;H0,H1;!$(NC=O):1])[c;H1][c;H1]1>>["
"N:1]",
"Ts", "tosyl", "Cc1ccc(cc1)S(NO)(=O)=O>>NO"},
{"amine",
"[C;R0][C;R0]([C;R0])([O;R0][C;R0](=[O;R0])[NX3;H0,H1:1])C>>[N:1]",
"Boc", "tert-butyloxycarbonyl",
"N(C(=O)OC(C)(C)C)Cc1ccccc1NC(=O)OC(C)(C)C>>NCc1ccccc1N"},
{"amine", "[N;H0,H1:1]C(=O)C(F)(F)F>>[N:1]", "TFA", "trifluoroacetyl",
"ONC(=O)C(F)(F)F>>NO"},
{"amine",
"[NX3;H0,H1:1]C(=O)c1[c;H1][c;H1][c;H1][c;H1][c;H1]1>>[N:1]",
"Bz", "benzoyl", "ONC(=O)c1ccccc1>>NO"},
{"amine", "[NX3;H0,H1:1][#6](=O)-[#8]-[#6]-[#6]-1-c2ccccc2-c2ccccc-12>>[N:1]",
"Fmoc", "9-fluorenylmethyloxycarbonyl",
"CN(C)C(=O)OCC1C2=CC=CC=C2C2=C1C=CC=C2>>CNC"},
{"amine",
"[NX3;H0,H1;!$(NC=O):1][C;H2]c1[c;H1][c;H1][c;H1][c;H1][c;H1]1>>[N:1]",
"Bn", "benzylamine",
"CN(C)Cc1ccccc1>>CNC"},
{"amine", "[NX3;H0,H1:1][C;R0](=O)[C;H3]>>[N:1]", "Ac",
"acetamide",
"N(C)(C)C(=O)C>>CNC"},
{"amine",
"[NX3;H0,H1:1][C;R0](=O)[O;R0][C;R0]c1[c;H1][c;H1][c;H1][c;H1][c;H1]1>>[N:1]",
"Cbz", "carbobenzyloxy",
"N(C)(C)C(=O)OCc1ccccc1>>CNC"},
{"carbonyl",
"[#6,#1:1][C:2]([#6,#1:3])([#8:4][#6])([#8][#6])>>[*:1][C:2]([*:3])[#8:4]",
"Acetyl/Ketal", "Acetal/Ketal",
"O=C(OC)C1CCC(OC2)(OC2)CC1>>COC(=O)C1CCC(O)CC1"},
};
return deprotections;
}
const unsigned int MAX_DEPROTECTIONS = 100;
std::unique_ptr<ROMol> deprotect(
const ROMol &mol, const std::vector<DeprotectData> &deprotections) {
std::vector<std::string> deprotections_used;
bool something_happened = true;
auto m = boost::make_shared<ROMol>(mol);
while (something_happened) {
something_happened = false;
for (auto &deprotect : deprotections) {
if (!deprotect.isValid()) {
// error and contine;
continue;
}
for (auto &prods : deprotect.rxn->runReactant(m, 0)) {
m = prods[0];
try {
RDLog::BlockLogs blocker;
MolOps::sanitizeMol(*dynamic_cast<RWMol *>(m.get()));
} catch (MolSanitizeException &) {
continue;
}
deprotections_used.push_back(deprotect.abbreviation);
if (deprotections_used.size() >= MAX_DEPROTECTIONS) {
BOOST_LOG(rdErrorLog)
<< "Too many deprotections, halting..." << std::endl;
} else
something_happened = true;
break;
}
}
}
m->setProp("DEPROTECTIONS", deprotections_used);
m->setProp<int>("DEPROTECTION_COUNT", deprotections_used.size());
return std::unique_ptr<ROMol>(new ROMol(*m.get()));
};
} // namespace Deprotect
} // namespace RDKit
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