B Is Selected from the Group Consisting of R.Sub.4 -R.Sub.5 -R.Sub.6
Initial material, as described in claim 1, to be used in the reactor after the method and process as described in claim 1, where the liquid material is a mixture of liquid states of elements generally known as “metals” (Alkali metals, Alkaline earth metals, transition metals, actinides, lanthanides, poor metals) and metaloids of the periodic table, where the activity modulating compound is of the formula A-B-D-E-G-J or the chemical acceptable liquid thereof wherein the groups A through J have the values:
A is R.sub.1 -R.sub.2 -R.sub.3 ;
B is selected from the group consisting of R.sub.4 -R.sub.5 -R.sub.6,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
D is selected from the group consisting of R.sub.7 -R.sub.8 -R.sub.9,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
E is selected from the group consisting of R.sub.10 -R.sub.11 -R.sub.12,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
G is selected from the group consisting of R.sub.13 -R.sub.14 -R.sub.15,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
J is selected from the group consisting of R.sub.16 -R.sub.17 -R.sub.18,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
L is selected from the group consisting of R.sub.19 -R.sub.20 -R.sub.21,
R.sub.31, R.sub.32, R.sub.35 and R.sub.37 ;
M is a valence bond, or is selected from the group consisting of R.sub.22
-R.sub.23 -R.sub.24, R.sub.31, R.sub.32, R.sub.35, and R.sub.37 ;
Q is R.sub.25 -R.sub.26 -R.sub.27 ; or
B and D, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ;
D and E, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ;
E and G, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ;
G and J, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ;
J and L, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ;
L and M, taken together, optionally represent a group selected from the
group consisting of R.sub.33, R.sub.34, R.sub.38, R.sub.39, R.sub.40,
R.sub.41, R.sub.42, R.sub.43, and R.sub.44 ; and one or more of the groups
R.sub.5 -R.sub.6 -R.sub.7, R.sub.8 -R.sub.9 -R.sub.10, R.sub.11 -R.sub.12
-R.sub.13, R.sub.14 -R.sub.15 -R.sub.16, R.sub.17 -R.sub.18 -R.sub.19,
R.sub.20 -R.sub.21 -R.sub.22, and R.sub.23 -R.sub.24 -R.sub.25,
independently may optionally represent R.sub.36 ;
wherein
(a) R.sub.1 is selected from the group consisting of alkali metals (Li, Na, K, Rb, Cs, Fr)
(b) R.sub.2 is selected from the group consisting of Alkaline earth metals (Be, Mg, Ca, Sr, Ba, Ra)
(c) R.sub.3 is selected from the group consisting of transition metals (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Rf, Db, Sg, Bh, Hs, Mt, Ds, Rg, Uub);
(d) R.sub.4 is selected from the group consisting of poor metals (Al, Ga, In, Sn, Ti, Pb, Bi, Uut, Uuq, Uup, Uuh);
(e) R.sub.5 is selected from the group consisting of actinides (Ac, Th, Pa, U, Np, Pu, Am, Cm, Bk, Cf, Es, Fm, Md, No, Lr);
(f) R.sub.6 is selected from the group consisting of lanthanides (La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu);
(g) R.sub.8 is a liquid containing hydrogen;
(h) R.sub.8 is a liquid containing hydrogen;
(i) R.sub.8 is a liquid containing hydrogen;
R.sub.5 is selected from the group consisting of >CR.sub.201 R.sub.202,
>NR.sub.203 >C.dbd.CR.sub.205 R.sub.206, existing in either the Z- or
E-configuration, and substituted cyclopropyl of the formula
##STR28##
(f) R.sub.6, R.sub.9, R.sub.12, R.sub.15, and R.sub.18 are independently
selected from the group consisting of >C.dbd.O, >CH.sub.2, --CH.sub.2
C(O)--, --NHC(O)--, >C.dbd.S, >SO.sub.2, and >P(O)X where X is selected
from hydroxy, alkoxy, amino, alkylamino and dialkylamino;
(g) R.sub.7, R.sub.10, R.sub.13, R.sub.16, R.sub.19, and R.sub.22, are
independently selected from the group consisting of >CH.sub.2 and
>NR.sub.50 where R.sub.50 is selected from the group consisting of
hydrogen, lower alkyl, arylalkyl, aryl, hydroxy and alkoxy;
(h) R.sub.21, and R.sub.24 are independently selected from the group
consisting of >C.dbd.O, --CH.sub.2 C(O)--,--NHC(O)--, >C.dbd.S, >SO.sub.2,
and >P(O)X where X is selected from the group consisting of hydroxy,
alkoxy, amino, alkylamino and dialkylamino, with the proviso that when
R.sub.22 -R.sub.23 -R.sub.24 is present, R.sub.21 is >CH.sub.2
(i) R.sub.8 is selected from the group consisting of >CR.sub.210 R.sub.211,
>NR.sub.213, >C.dbd.CR.sub.215 R.sub.216, existing in either the Z- or
E-configuration, and substituted cyclopropyl of the formula
##STR29##
(j) R.sub.11 is selected from the group consisting of >CR.sub.220
R.sub.221, >NR.sub.223, >C.dbd.CR.sub.225 R.sub.226, existing in either
the Z- or E-configuration, and substituted cyclopropyl of the formula
##STR30##
(k) R.sub.14 is selected from the group consisting of >CR.sub.230
R.sub.231, >NR.sub.233, >C.dbd.CR.sub.235 R.sub.236, existing in either
the Z- or E-configuration, and substituted cyclopropyl of the formula
##STR31##
(l) R.sub.17 is selected from the group consisting of >CR.sub.301
R.sub.302, >NR.sub.303, >C.dbd.CR.sub.305 R.sub.306, existing in either
the Z- or E-configuration, and substituted cyclopropyl of the formula
##STR32##
(m) R.sub.20 is selected from the group consisting of >CR.sub.310
R.sub.311, >C.dbd.CR.sub.315 R.sub.316, existing in either the Z- or
E-configuration, and substituted cyclopropyl of the formula
##STR33##
(n) R.sub.23 is selected from the group consisting of >CR.sub.320
R.sub.321, >C.dbd.CR.sub.325 R.sub.326, existing in either the Z- or
E-configuration, and substituted cyclopropyl of the formula
##STR34##
(o) R.sub.25 is selected from the group consisting of >O, and >NR.sub.109
where R.sub.109 is selected from the group consisting of hydrogen, lower
alkyl, and arylalkyl;
(p) R.sub.26 is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl and >NR.sub.110 where R.sub.110 is selected from the
group consisting of hydrogen, lower alkyl, or arylalkyl with the provisos
that
(i) when R.sub.25 is >O then R.sub.26 is lower alkyl, and
(ii) when R.sub.26 is hydrogen, lower alkyl, or arylalkyl, then R.sub.27 is
absent;
(q) R.sub.27 is selected from the group consisting of hydrogen, and aryl;
(r) R.sub.31 is
##STR35##
where m and n are integers independently selected from 0, 1 and 2; (s)
R.sub.32 is
##STR36##
where p and q are integers independently selected from 0, 1 and 2; (t)
R.sub.33 is
##STR37##
where t and v are integers independently selected from 0, 1, 2 and 3; (u)
R.sub.34 is
##STR38##
where r and s are integers independently selected from 0, 1, 2 and 3; (v)
R.sub.35 is
##STR39##
where f is an integer of 0 to 2, X is selected from the group consisting
of >C.dbd.O and --CH.sub.2 -- and R is selected from the group consisting
of hydrogen and lower alkyl, with the provisos that
(i) when f is 0, X is at C-2 and R is at C-3 or C-4;
(ii) when f is 1, X is at C-2 and R is at C-3, C-4 or C-5 and C-3,4 are
saturated or unsaturated;
(iii) when f is 2, X is at C-2, C-3 or C-4 and R is at C-2, C-3, C-4, C-5
or C-6 when the position is unoccupied by X and C-3,4 or C-4,5 are
saturated or unsaturated; and
(w) R.sub.36 is
##STR40##
where g is an integer of from 0 to 3; (x) R.sub.37 is
##STR41##
wherein h is 1 and j is 0 or 1; (y) R.sub.38 is
##STR42##
where k is an integer of from zero to two; (ae) R.sub.44 is
##STR43##
(af) R.sub.1 and R.sub.2, taken together, optionally represent a group
selected from the group consisting of aryl, and hydrogen;
(ag) R.sub.1, R.sub.2 and R.sub.3, taken together, optionally represent a
group selected from the group consisting of lower alkyl, arylalkyl,
alkenyl, hydrogen, and an N-terminal protecting group;
(ah) R.sub.6 and R.sub.7 ; R.sub.9 and R.sub.10 ; R.sub.12 and R.sub.13 ;
R.sub.15 and R.sub.16 ; R.sub.18 and R.sub.19 ; R.sub.21 and R.sub.22 ;
each pair taken together, optionally and independently represent a group
selected from the group consisting of --C(O)NH--, >CH.sub.2,
--(CH.sub.2).sub.3 --, --CH.dbd.CH--, --CH(OH)--,
--C.tbd.C--,--C(.dbd.CH.sub.2)CH.sub.2 --, --CH(OH)CH.sub.2 --, --C(O)O--,
--C(O)S--, --CH.sub.2 C(O)O--, --CH.sub.2 C(O)S--, --CH.sub.2 O--,
--CH.sub.2 S--, and --NHC(O)--, with the provisos that
(i) at least one of said pair, taken together, must be other than
--C(O)NH--; and
(ii) when R.sub.5 is >NR.sub.203 or >C.dbd.CR.sub.205 R.sub.206, R.sub.6
and R.sub.7, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 ;
(iii) when R.sub.8 is >NR.sub.213 or >C.dbd.CR.sub.215 R.sub.216, R.sub.9
and R.sub.10, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --;
(iv) when R.sub.11 is >NR.sub.223 or >C.dbd.CR.sub.225 R.sub.226, R.sub.12
and R.sub.13, taken together represent --C(O)NH-- or --C(O)NCH.sub.3 --;
(v) when R.sub.14 is >NR.sub.233 or >C.dbd.CR.sub.235 R.sub.236, R.sub.15
and R.sub.16, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --;
(vi) when R.sub.17 is >NR.sub.303 or >C.dbd.CR.sub.305 R.sub.306, R.sub.18
and R.sub.19, taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --;
(vii) when R.sub.20 is >C.dbd.CR.sub.315 R.sub.316, R.sub.21 and R.sub.22,
taken together, represent --C(O)NH-- or --C(O)NCH.sub.3 --;
(ai) R.sub.26 and R.sub.27, taken together, optionally represent hydrogen,
with the proviso that when R.sub.25 is >O then R.sub.26 and R.sub.27,
taken together, represent hydrogen, lower alkyl, or arylalkyl;
(aj) R.sub.99, R.sub.202, R.sub.211, R.sub.221, R.sub.231, R.sub.302,
R.sub.311, and R.sub.321 are independently selected from the group
consisting of hydrogen, arylalkyl with the proviso that for R.sub.302 and
R.sub.311, arylalkyl is limited to benzyl when R.sub.19 -R.sub.20
-R.sub.21 or R.sub.22 -R.sub.23 -R.sub.24 respectively represent an
L-arginyl residue, and lower alkyl;
(ak) R.sub.100 is selected from the group consisting of hydrogen, and lower
alkyl;
(al) R.sub.201 is selected from the group consisting of hydrogen, lower
alkyl, alkenyl, aryl, arylalkyl, (cycloalkyl)alkyl, aminoalkyl,
amidoalkyl, hydroxyalkyl, guanidinoalkyl, carboxyalkyl,
(carboxyamido)alkyl, (carboxyhydrazino)alkyl, ureidoalkyl,
(heterocyclic)alkyl, (thioalkoxy)alkyl, and sulfhydrylalkyl;
(am) R.sub.201 and R.sub.202, R.sub.210 and R.sub.211, R.sub.220 and
R.sub.221, R.sub.230 and R.sub.231, R.sub.301 and R.sub.302, R.sub.310 and
R.sub.311, R.sub.320 and R.sub.321, each pair taken together,
independently may optionally represent --(CH.sub.2).sub.z -- where z is an
integer of from 2 to 6;
(an) R.sub.203 is selected from the group consisting of hydrogen, lower
alkyl, alkenyl, arylalkyl, (cycloalkyl)alkyl, aminoalkyl, amidoalkyl,
hydroxyalkyl, guanidinoalkyl, carboxyalkyl, (carboxyamido)alkyl,
(carboxyhydrazino)alkyl, ureidoalkyl, (heterocyclic)alkyl,
(thioalkoxy)alkyl, and sulfhydrylalkyl with the proviso that R.sub.203 may
not be a vinyl group nor have a heteroatom directly attached to the
nitrogen or separated from it by one methylene unit;
(ao) R.sub.205, R.sub.206, R.sub.215, R.sub.216, R.sub.225, R.sub.226,
R.sub.235, R.sub.236, R.sub.305, and R.sub.306 are independently selected
from the group consisting of hydrogen, lower alkyl, aryl, arylalkyl,
wherein arylalkyl is excluded from R.sub.305 and R.sub.306 when R.sub.19
-R.sub.20 -R.sub.21 represents an L-arginyl residue, (cycloalkyl)alkyl,
amidoalkyl, wherein benzoyl amides and their heterocyclic variants are
excluded from R.sub.305 and R.sub.306 when R.sub.19 -R.sub.20 -R.sub.21
represents an L-arginyl residue (carboxyamido)alkyl, wherein aniline
amides and their heterocyclic variants are excluded from R.sub.305 and
R.sub.306 when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl
residue; ureidoalkyl, and (heterocyclic)alkyl, wherein when R.sub.19
-R.sub.20 -R.sub.21 represents an L-arginyl residue, then the heterocycle
at from R.sub.305 and R.sub.306 can only be separated by one methylene
unit from the alpha-carbon;
(ap) R.sub.210 selected from the group consisting of lower alkyl,
arylalkyl, aminoalkyl,and guanidinoalkyl;
(aq) R.sub.213 is selected from the group consisting of lower alkyl,
arylalkyl, aminoalkyl, and guanidinoalkyl with the proviso that R.sub.213
may not be a vinyl group nor have a heteroatom directly attached to the
nitrogen or separated from it by one methylene unit;
(ar) R.sub.220 is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl, (cycloalkyl)alkyl, and guanidinoalkyl;
(as) R.sub.223 is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl, (cycloalkyl)alkyl,and guanidinoalkyl, with the proviso
that R.sub.223 may not be a vinyl group nor have a heteroatom directly
attached to the nitrogen or separated from it by one methylene unit;
(at) R.sub.230 is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl, and (cycloalkyl)alkyl;
(au) R.sub.233 is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl, and (cycloalkyl)alkyl with the proviso that R.sub.233
may not be a vinyl group nor have a heteroatom directly attached to the
nitrogen or separated from it by one methylene unit;
(av) R.sub.301 is independently selected from the group consisting of
hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is
limited to benzyl, when R.sub.19 -R.sub.20 -R.sub.21 represents an
L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and
arylalkyl amines are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents
an L-arginyl residue; amidoalkyl, wherein benzoyl amides and their
heterocyclic variants are excluded when R.sub.19 -R.sub.20 -R.sub.21
represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl;
carboxyalkyl; (carboxyamido)alkyl, wherein aniline amides of aspartyl
residues and heterocyclic variants are excluded when R.sub.19 -R.sub.20
-R.sub.21 represents an L-arginyl residue; carboxyhydrazino)alkyl;
ureidoalkyl; (heterocyclic)alkyl, wherein when R.sub.19 -R.sub.20
-R.sub.21 represents an L-arginyl residue, then the heterocycle can only
be separated by one methylene unit from the alpha-carbon;
(thioalkoxy)alkyl, and sulfhydrylalkyl;
(aw) R.sub.303 is independently selected from the group consisting of lower
alkyl, arylalkyl, wherein arylalkyl is limited to benzyl when R.sub.19
-R.sub.20 -R.sub.21 represents an L-arginyl residue, and
(cycloalkyl)alkyl, with the proviso that R.sub.303 may not be a vinyl
group or have a heteroatom directly attached to the nitrogen or separated
from it by one methylene unit;
(ax) R.sub.304 is independently selected from the group consisting of
hydrogen; lower alkyl; alkenyl; aryl, arylalkyl, wherein arylalkyl is
excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl
residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and arylalkyl amines
are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl
residue; amidoalkyl, wherein benzoyl amides and their heterocyclic
variants are excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an
L-arginyl residue; hydroxyalkyl; guanidinoalkyl; carboxyalkyl;
(carboxyamido)alkyl, wherein aniline amides and heterocyclic variants are
excluded when R.sub.19 -R.sub.20 -R.sub.21 represents an L-arginyl
residue; (carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl,
wherein (heterocyclic)alkyl is excluded when R 19-R.sub.20 -R.sub.21
represents an L-arginyl residue; (thioalkoxy)alkyl; and sulfhydrylalkyl;
(ay) R.sub.307 and R.sub.317 are independently selected from hydrogen;
lower alkyl; aryl and arylalkyl, wherein arylalkyl is excluded for
R.sub.307 and R.sub.317 when R.sub.19 -R.sub.20 -R.sub.21 and R.sub.22
-R.sub.23 -R.sub.24 respectively represent an L-arginyl residue;
(az) R.sub.310 is independently selected from the group consisting of
hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is
limited to benzyl when R.sub.22 -R.sub.23 -R.sub.24 represents an
L-arginyl residue; (cycloalkyl)alkyl; aminoalkyl, aryl and arylalkyl
amines are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an
L-arginyl residue; amidoalkyl, wherein benzoyl amides and their
heterocyclic variants are excluded, when R.sub.22 -R.sub.23 -R.sub.24
represents an L-arginyl residue; hydroxyalkyl; guanidinoalkyl;
(carboxyamido)alkyl, wherein aniline amides of aspartyl residues and
heterocyclic variants are excluded when R.sub.22 -R.sub.23 -R.sub.24
represents an L-arginyl residue; (carboxyhydrazino)alkyl; ureidoalkyl;
(heterocyclic)alkyl, wherein when R.sub.22 -R.sub.23 -R.sub.24 represents
an L-arginyl residue, then the heterocycle can only be separated by one
methylene unit from the alpha-carbon; and sulfhydrylalkyl;
(ba) R.sub.312 is independently selected from the group consisting of
hydrogen; lower alkyl; alkenyl; aryl; arylalkyl, wherein arylalkyl is
excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl
residue; (cycloalkyl)alkyl; aminoalkyl, wherein aryl and arylalkyl amines
are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl
residue; amidoalkyl, wherein benzoyl amides and their heterocyclic
variants are excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an
L-arginyl residue; hydroxyalkyl; guanidinoalkyl; carboxyalkyl;
(carboxyamido)alkyl, wherein aniline amides and heterocyclic variants are
excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl
residue; (carboxyhydrazino)alkyl; ureidoalkyl; (heterocyclic)alkyl,
wherein (heterocyclic)alkyl is excluded when R.sub.22 -R.sub.23 -R.sub.24
represents an L-arginyl residue; (thioalkoxy)alkyl; and sulfhydrylalkyl;
(bb) R.sub.315 and R.sub.316 are independently selected from the group
consisting of hydrogen, lower alkyl, arylalkyl, wherein arylalkyl is
excluded when R.sub.22 -R.sub.23 -R.sub.24 represents an L-arginyl
residue, and (cycloalkyl)alkyl;
(bc) R.sub.310 is is selected from the group consisting of hydrogen, lower
alkyl, arylalkyl, alkenyl, (cycloalkyl)alkyl, aminoalkyl, and
guanidinoalkyl;
(bd) R.sub.325 and R.sub.326 are independently selected from the group
consisting of hydrogen, lower alkyl, aryl, arylalkyl, and
(cycloalkyl)alkyl;
all of the foregoing with the provisos that
(i) when more than one sulfhydrylalkyl is present in the compound, the
compound exists in the oxidized disulfide form producing a cyclic
molecule, or the two sulfhydryl moieties are connected by a C.sub.2 to
C.sub.8 alkylene chain and
(ii) when the compound contains a free amino group and carboxyl group, they
can be cyclized to give the corresponding lactam.