Note: Claims are shown in the official language in which they were submitted.
-24-
We claim:
1. A compound of Formula III
Image
wherein
Ar is selected from the group consisting of phenyl, any
simple unsubstituted aromatic, simple substituted aromatic,
substituted heteroaromatic group, unsubstituted
heteroaromatic group, heterocyclic, C1,-C12 alkyl, C2-C12
alkenyl, C2-C12 alkynyl, NR51R52, COR52, OR53, and Formula Ar'
Image
R51 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R52 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R53 is selected from the group consisting of C1,-C12 alkyl;
R54 is selected from the group consisting of hydrogen, C -C
alkyl, C1-C6 alkyl(R57' R57'' R5'''), simple unsubstituted
aromatlc, simple substituted aromatic, heterocyclic, phenyl,
halogen, 4-(tert-butyldimethylsiloxy)-benzyltriphenylphosophonium,
COOR57, PO3H, SO3H, SO2R58,
N(R59)R60, NHOR61, NHCHR61, CN, NO, halogen, OR6, CH2(O)R62', -
-25-
Image
CH2OC(O) R 95, CH2N (R 96) R 96', COR I00, (C1,-C6alkyl ) OR 100, , and
SR 63;
R 95 is selected from the group consisting of -R 98 NH3;
R 96 and R 96' are each independently selected from the group
consisting of hydrogen and C1-C6 alkyl, -R 97 NH , and -R NR
R 99';
R 97 is selected from the group consisting of C1,-C6 alkyl;
R 98 is selected from the group consisting of C1,-C6 alkyl;
R 99 is C1-C6 alkyl;
R 99' and R 99'' are each independently selected from the group
consisting of hydrogen and C1-C6 alkyl;
R 100 is selected from the group consisting of hydrogen, and
Si (R 100 R 102 R 103);
R 101 is Cl-C6 alkyl;
R 102 is C1-C6 alkyl;
R 103 is Cl-C6 alkyl;
R l04 is selected from the group consisting of C(O)C1-C6
alkylN(R 106)(R 59)R 60, C(O)C1-C6 alkylN +, fused bicyclic, and
NHR 105 N ( R 106 ) ( R 59)R 60;
R 105 is selected from the group consisting of C(O)C1-C6 alkyl,
C1-C6 alkyl;
R 106 is selected from the group consisting of hydrogen, C1-C6
alkyl, C(O)OR 107;
R 107 is selected from the group consisting of hydrogen, C1-C6
alkyl, CR108 R 109 R 110
R 108 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 109 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 110 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
-26-
R 111 is selected from the group consisting of hydrogen, C1-C6
alkyl, and C(O)OR 107
R55 is selected from the group consisting of hydrogen, C1-C6
alkyl, C(R 57' R 57'' R 57'''), simple unsubstituted aromatic, simple
substituted aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58,
NR 59 R 60, NHOR 6l, NHCHR 61', CN, NO2, halogen, OR62, and SR63;
R 56 is selected from the group consisting of hydrogen, C1-C6
alkyl, C(R 57' R 57'' R 57''' ), simple unsubstituted aromatic, simple
substituted aromatic, phenyl, COOR 57, PO3H, SO3H, SO R 58,
NR 59 R 60, NHOR 61, NHCHR 61', (C1-C6)alkylNR 59R , CN, NO2, halogen,OR 104 CR 104 OR 62, and SR63;
R 57 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R57' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R 57'' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R 57''' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R 58 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R59 is selected from the group consisting cf hydrogen,
(C1-C6) alkyl, tert-butoxycarbonyl, carbo-tert-butoxy (t-BOC)
and fluorenylmethoxycarbonyl (FMOC);
R60 is selected from the group consisting of hydrogen and
(C1-C6) alkyl;
R 61' is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65', and fluorenylmethoxycarbonyl (FMOC);
R 61' is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65' and fluorenylmethoxycarbonyl (FMOC);
R 62 is selected from hydrogen, and C1-C6 alkyl;
R 62' is selected from hydrogen, OH, OR 62, and C1-C6 alkyl;
R 63 is selected from hydrogen and C1-C6 alkyl;
-27-
R 64 is selected from the group consisting of hydrogen,
(C1-C6) alkyl, CH2NR 66 R 67;
R 65 is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycarbonyl (FMOC);
R 65' is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycarbonyl (FMOC);
R 66 is selected from the group consisting of hydrogen and
C1-C6 alkyl and fluorenylmethoxycarbonyl (FMOC);
R 67 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 3 is a lower alkyl group;
R 4 is H or OH;
R 5 is H or OH;
R 4 and R 5 may be taken together to form a second bond
between C 13 and C 14;
R 6 is a substituent selected from the group consisting of
benzyl, hydroxybenzyl, alkoxybenzyl, halohydroxybenzyl,
dihalohydroxybenzyl, haloalkoxybenzyl, or
dihaloalkyoxybenzyl group, B-ring heteroaromatic,
substituted heteroaromatic, B-ring
(C1-C6)alkyl, (C3-C8)cycloalkyl, substituted C3-C8 cycloalkyl,
substituted (C1-C6)alkyl, a group of the formula III'
Image
and a group of the formula III'':
Image
-28-
R 7 is selected from the group consisting of NR 51 R 52, R 53 NR 51 R 53,
OR 53, H and a lower alkyl group; R 51 and R 52 are independently
selected from the group consisting of C1-C3 alkyl; R 53 is C1-C3
alkyl;
R 8 is H or a lower alkyl group; or
R 7 and R 8 can form a cyclopropyl ring;
R 9 is selected from the group consisting of H, a lower alkyl
group, unsaturated lower alkyl, lower alkyl-C3-C5
cycloalkyl, and benzyl;
R 10 is H or a lower alkyl group;
R 11 is selected from the group consisting of hydrogen, OH,
lower alkyl group, substituted phenyl, benzyl, substituted
benzyl and phenyl;
R 15, R 16, and R 17 are each independently selected from the
group consisting of hydrogen, OR 18, halo, NR 18' R 19', NO2,
OPO3H2, OR 19 phenyl, SCH2phenyl, CONH2, C02H, PO3H, SO2R 23, and
ZZ;
R 18 is selected from the group consisting of hydrogen, aryl,
C1-C6 alkyl, C(O)R 90 and fluorenylmethoxycarbonyl (FMOC);
R 18 is selected from the group consisting of hydrogen,
C1-C6)alkyl and C(O)R 90;
R 19 is C1-C6 alkyl, C(O)R 90'' and fluorenylmethoxycarbonyl
(FMOC );
R 19' is selected from the group consisting of hydrogen,
C1-C6)alkyl, and C(O)R 90''';
R 90, R 90', R 90'' , and R 90''' are each independently selected from
the group consisting of hydrogen, (C1-C6)alkyl, OR 9l and
aryl;
R 91 is selected from the group consisting of (C1-C6)alkyl,
aryl, and hydrogen;
R 23 is selected from the group consisting of hydrogen and
(C1-C3 ) alkyl;
R 30 is hydrogen or C1-C6 alkyl; or
-29-
R 30 may be taken together with the N at C-ll to form a three
to seven membered cyclic ring;
Image
R 50 is hydrogen or
n is 0, 1, or 2;
m is 0, 1, or 2;
p is 0, 1,or 2;
X is selected from the group consisting of O, C, S, NH and
alkylamino;
Y is selected from the group consisting of C, O, NH, S, SO,
SO2 and alkylamino;
Z is selected from the group consisting of -(CH2)n-, - (CH2)p-
O-(CH2)m- and (C3-C5) cycloalkyl;
ZZ is selected from the group consisting of a simple
unsubstituted aromatic group and a slmple substituted
aromatic group; or
a pharmaceutically acceptable salt or solvate thereof.
2. A compound of Claim 1 wherein the compound of
Formula III is defined as follows:
Image
wherein
Ar is phenyl or any simple unsubstituted or substituted
aromatic or heteroaromatic group, C1-C12 alkyl, C1-C12
alkene, C1-C12 alkyne, NR 5l R 52, OR 53, Formula Ar'
-30-
Image
R 51 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 52 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 53 is selected from the group consisting of C1-C12 alkyl;
R 54 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58
NR 59 R 60, NHOR 61, NHCHR 61' , CN, NO2, halogen, OR62, and SR 63;
R 55 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58'
NR 59 R 60, NHOR 61, NHCHR 61' , CN, NO2, halogen, OR 62, and SR 63;
R 56 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COCR 57, PO3H, SO3H, SO2R 58,
NR 59 R 60, NHOR 61, NHCHR 61' , CN, NO2, halogen, OR 62, and SR 63;
R 57 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R 58 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R 59 is selected from the group consisting of hydrogen,
C1-C6) alkyl and fluorenylmethoxycaronyl (FMOC);
R 60 is selected from the group consisting of hydrogen and
(C1-C6) alkyl;
R 61 is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65 and fluorenylmethoxycaronyl (FMOC);
R 61' is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65 and fluorenylmethoxycaronyl (FMOC);
R 62 is selected from hydrogen and C1-C6 alkyl;
R 63 is selected form hydrogen and C1-C6 alkyl;
R 64 is selected from the group consisting of hydrogen,
C1-C6) alkyl, CH2NR 66 R 67
-31-
R 65 is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycaronyl (FMOC);
R 66 is selected from the group consisting of hydrogen and
C1-C6 alkyl and fluorenylmethoxycaronyl (FMOC);
R 67 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 3 is a lower alkyl group;
R 4 is H or OH;
R 5 is H or OH;
R 4 and R 5 may be taken together to form a second bond
between C13 and C14;
R 6 is selected from the group consisting of benzyl,
hydroxybenzyl, alkoxybenzyl, halohydroxybenzyl,
dihalohydroxybenzyl, haloalkoxybenzyl, or dihaloalkoxybenzyl
group, B-ring heteroaromatic, substituted heteroaromatic, B-ring
(C1-C6)alkyl, (C3-C8)cycloalkyl, substituted C3-C8
cycloalkyl, substituted (C1-C6)alkyl, a group of the formula
III':
Image
and a group of the formula III'':
Image
R 7 is H or a lower alkyl group;
R 8 is H or a lower alkyl group;
R 9 is H or a lower alkyl group;
R 10 is H or a lower alkyl group;
R 11 is selected from the group consisting of H, OH, simple
alkyl, phenyl, substituted phenyl, benzyl, and substltuted
benzyl;
-32-
R 15, R 16, and R 17 are each independently selected from the
group consisting of hydrogen, (C1-C6)alkyl, OR 18, halo,
NR 18' R 19' , NO2, OPO4H2, OR 19 phenyl, SCH2phenyl, CONH2, CO2H,
PO3H2, So2R23, and ZZ;
R 18 is selected from the group consisting of hydrogen, aryl,
and C1-C6 alkyl;
R 18 is selected from the group consisting of hydrogen and
(C1-C6)alkyl;
R 19 is C1-C6 alkyl;
R 19' is selected from the group consisting of hydrogen and
(C1-C6)alkyl;
R 23 is selected from the group consisting of hydrogen and
(C1-C3)alkyl;
R 30 is hydrogen or C1-C6 alkyl;
Image
R 50 is hydrogen or
n is 0, 1, or 2;
p is 0, 1, or 2;
m is 0, 1, or 2;
q is 2, 3, or 4;
X is O, NH or alkylamino;
Y is C, O, NH, S, SO, SO2 or alkylamino;
Z is selected from the group consisting of -(CH2) n-,
- ( CH2 ) p-O- ( CH2 ) m- and (C3-C5)cycloalkyl;
ZZ is selected from the group consisting of an aromatic
group and a substituted aromatic group; or
a pharmaceutically acceptable salt thereof.
3. A compound of Claim 1 wherein Ar is selected
from the group consisting of phenyl, aromatic, or simple
substituted aromatic.
4. A compound of Claim 2 wherein Ar is a
parafluoro substituted phenyl ring.
5. A compound of Claim 1 wherein R 30 is hydrogen,
R 7 and R 8 are each methyl, X is O, Y is O, and R 50 is a group
Image
of the formula .
-33-
6. A compound of Claim l wherein R 30 is hydrogen,
one of R 7 and R 8 is methyl, X is O, Y is O, and R 50 is a
Image
group of the formula
7. A process for preparing a compound of Formula
II
Image
wherein
Ar is selected from the group consisting of phenyl, any
simple unsubstituted aromatic, simple substituted aromatic,
substituted heteroaromatic group, unsubstituted
heteroaromatic group, heterocyclic, C1-C12 alkyl, C2-C12
alkenyl, C2-C12 alkynyl, NR 51 R 52, COR 52, OR 53, and Formula Ar'
Image
R 51 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 52 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 53 is selected from the group consisting of C1-C12 alkyl;
R 54 is selected from the group consisting of hydrogen, C1-C6
alkyl, C1-C6alkyl(R 57' R 57'' R 57'''), simple unsubstituted
aromatic, simple substituted aromatic, heterocyclic, phenyl,
halogen, 4-(tert-butyldimethylsiloxy)-benzyltriphenylphosophonium,
-34 -
X COOR 57, PO3H, SO3H, SO2R 58,
N (R 59) R 60, NHOR 61, NHCHR 61', CN, NO2, halogen, OR 62, CH2 (O) R 62',
Image
CH2OC (O) R 95, CH2N (R 96) R 96', COR 100, (C1,-C6alkyl) OR 100, , and
SR 63;
R 95 iS selected from the group consisting of -R 96 NH3;
R 96 and R 96' are each independently selected from the group
consisting of hydrogen and C1-C6 alkyl, -R 97 NH3, and -R 99 NR99'
R 99'';
R 97 is selected from the group consisting of C1-C6 alkyl;
R 98 is selected from the group consisting of C1-C6 alkyl;
R 99 is C1-C6 alkyl;
R 99' and R 99'' are each independently selected from the group
consisting of hydrogen and C1-C6 alkyl;
R 100 is selected from the group consisting of hydrogen, and
Si (R 101 R 102 R 103);
R 101 is C1-C6 alkyl;
R 102 i s C1-C6 alkyl;
R 103 is C1-C6 alkyl;
R 104 is selected from the group consisting of C (O) C1-C6
alkylN (R 106) (R 59) R 60, C (O) C1-C6 alkylN +, fused bicyclic, and
NHR 105N (R 106) (R 59) R 60;
R 105 is selected from the group consisting of C (O) C1-C6 alkyl,
C1-C6 alkyl;
R 106 is selected from the group consisting of hydrogen, C1-C6
alkyl, C (O) OR 107;
R 107 is selected from the group consisting of hydrogen, C1-C6
alkyl, CR 108 R 109 R 110
R 108 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 109 iS selected from the group consisting of hydrogen and
C1-C6 alkyl;
-35-
R 110 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 55 is selected from the group consisting of hydrogen, C1-C6
alkyl, C(R 57' R 57'' R 57'''), simple unsubstituted aromatic, simple
substituted aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58,
NR 59 R 60, NHOR 61, NHCHR 61', CN, NO2, halogen, OR 62, and SR 63;
R 56 is selected from the group consisting of hydrogen, C1-C6
alkyl, C(R 57' R 57'' R 57'''), simple unsubstituted aromatic, simple
substituted aromatic, phenyl, COOR 57, PO3H, SO3H, SO R 58,
NR 59 R 60, NHOR 61, NHCHR 61, (C1-C6) alkylNR 59 R 60, CN, NO2, halogen,
OR 104 CR 104 OR 62, and SR 63;
R 57 is selected from the group consisting of hydrogen and
C2-C12 alkyl;
R 57' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R 57'' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R57''' is selected from the group consisting of hydrogen,
halogen, and C1-C12 alkyl;
R 58 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 59 is selected from the group consisting of hydrogen,
(C1-C6) alkyl, tert-butoxycarbonyl, carbo-tert-butoxy (t-BOC)
and fluorenylmethoxycarbonyl (FMOC);
R 60 is selected from the group consisting of hydrogen and
(C1-C6) alkyl;
R 6l is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65' and fluorenylmethoxycarbonyl (FMOC);
R 6l' is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65' and fluorenylmethoxycarbonyl (FMOC);
R 62 is selected from hydrogen, and C1-C6 alkyl;
R 62' is selected from hydrogen, OH, OR 62, and C1-C6 alkyl;
R 63 is selected from hydrogen and C1-C6 alkyl;
-36-
R 64 is selected from the group consisting of hydrogen,
(C1-C6) alkyl, CH2NR 66 R 67;
R 65 is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycarbonyl (FMOC);
R 65' is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycarbonyl (FMOC);
R 66 is selected from the group consisting of hydrogen and
C1-C6 alkyl and fluorenylmethoxycarbonyl (FMOC);
R 67 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 3 is a lower alkyl group;
R 4 is H or OH;
R 5 is H or OH;
R 4 and R 5 may be taken together to form a second bond
between C 13 and C l4;
R 6 is a substituent selected from the group consisting of
benzyl, hydroxybenzyl, alkoxybenzyl, halohydroxybenzyl,
dihalohydroxybenzyl, haloalkoxybenzyl, or
dihaloalkyoxybenzyl group, B-ring heteroaromatic,
substituted heteroaromatic, B-ring
(C1-C6)alkyl, (C3-C8)cycloalkyl, substituted C3-C8 cycloalkyl,
substituted (C1-C6)alkyl, a group of the formula III'
Image
and a group of the formula III'':
Image
-37-
R 7 is selected from the group consisting of NR 51 R52,, R 53 NR51 R52,OR 53, H and a lower alkyl group; R 51 and R 52 are independently
selected from the group consisting of C1-C3 alkyl; R 53 is
C1-C3 alkyl;
R 8 is H or a lower alkyl group; or
R 7 and R 8 can form a cyclopropyl ring;
R 9 is selected from the group consisting of H, a lower alkyl
group, unsaturated lower alkyl, lower alkyl-C3-C5
cycloalkyl, and benzyl;
R 10 is H or a lower alkyl group;
R 11 is selected from the group consisting of hydrogen, OH,
lower alkyl group, substituted phenyl, benzyl, substituted
benzyl and phenyl;
R 15, R l6, and R 17 are each independently selected from the
group consisting of hydrogen, OR 18, halo, NR 18 R19, NO2,
OPO3H2, OR 13 phenyl, SCH2phenyl, CONH2 , CO2H, PO3H2, SO2R 23, and
ZZ;
R 18 is selected from the group consisting of hydrogen, aryl,
C1-C6 alkyl, C(O)R 90 and fluorenylmethoxycarbonyl (FMOC);
R 18 is selected from the group consisting of hydrogen,
(C1-C6)alkyl and C(O)R 90';
R 19 is C1-C6 alkyl, C(O)R 90'' and fluorenylmethoxycarbonyl
( FMOC );
R 19 is selected from the group consisting of hydrogen,
(C1-C6)alkyl, and C(O)R 90''';
R 90, R 90', R 90'' , and R 90''' are each independently selected from
the group consisting of hydrogen, (C1-C6)alkyl, OR 91' and
aryl;
R 91 is selected from the group consisting of (C1-C6)alkyl,
aryl, and hydrogen;
R 23 is selected from the group consisting of hydrogen and
( C1 -C3 ) alkyl;
R 30 is hydrogen or C1-C6 alkyl; or
-38-
R 30 may be taken together with the N at C-11 to form a three
to seven membered cyclic ring;
Image
R 50 is hydrogen or
n is 0, 1, or 2;
m is 0, 1, or 2;
p is 0, l,or 2;
X is selected from the group consisting of O, C, S, NH and
alkylamino;
Y is selected from the group consisting of C, O, NH, S, SO,
SO2 and alkylamino;
Z is selected fromt he group consisting of -(CH2)n-, -(CH)p-
O-(CH2)m- and (C3-C5) cycloalkyl;
ZZ is selected from the group consisting of a simple
unsubstituted aromatic group and a simple substituted
aromatic group;
comprising contacting a compound of Formula III
Image
-39-
with a solvent and a catalyst of the formula IV
Image
wherein M is selected from the group consisting of
hydrogen, Na, Li, K, and Cs;
x cat is selected from the group consisting of O,
N, and S;
y cat is selected from the group consisting of O,
N, and S;
R cat1 is selected from the group consisting of
C1-C6 alkyl and aryl;
R cat2 is selected from the group consisting of
C1-C6 alkyl and aryl.
8. A process of Claim 7 wherein the solvent is
selected from the group consisting of toluene,
N,N-dimethylformamide, ethyl acetate, tertrahydrofuran and
acetonitrile.
9. A process of Claim 7 wherein the Formula II
compound is defined as follows:
Image
wherein
Ar is phenyl or any simple unsubstituted or substituted
aromatic or heteroaromatic group, C1-C12 alkyl, C1-C12
alkene, C1-C12 alkyne, NR 51 R 52, OR 53, Formula Ar'
-40-
Image
Ar';
R 51 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 52 is selected from the group consisting of hydrogen and
C1-C3 alkyl;
R 53 is selected from the group consisting of C1-C12 alkyl;
R 54 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58
NR 59 R 60, NHOR 61, NHCHR 61' , CN, NO2, halogen, OR 62, and SR 63;
R 55 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COOR 57, PO3H, SO3H, SO2R 58,
NR 59 R 60, NHOR 61, NHCHR 61' , CN, NO2, halogen, OR 62, and SR 63;
R 56 is selected from the group consisting of hydrogen, C1-C6
alkyl, simple aromatic, phenyl, COOR57, PO3H, SO3H, SO2R 58,
NR 59 R 60, NHOR 61, NHCHR 61', CN, NO2, halogen, OR 62, and SR 63;
R 57 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R 58 is selected from the group consisting of hydrogen and
C1-C12 alkyl;
R 59 is selected from the group consisting of hydrogen,
(C1-C6) alkyl and fluorenylmethoxycaronyl (FMOC);
R 60 is selected from the group consisting of hydrogen and
(C1-C6) alkyl;
R 61 is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65 and fluorenylmethoxycaronyl (FMOC);
R 61' is selected from the group consisting of hydrogen, OR 64,
CH2NHR 65, NHR 65 and fluorenylmethoxycaronyl (FMOC);
R 62 is selected from hydrogen and C1-C6 alkyl;
R 63 is selected form hydrogen and C1-C6 alkyl;
R 64 is selected from the group consisting of hydrogen,
(C1-C6) alkyl, CH2NR 66 R 67
-41-
R 65 is selected from the group consisting of hydrogen and
C1-C6 alkyl, NH2, and fluorenylmethoxycaronyl (FMOC);
R 66 is selected from the group consisting of hydrogen and
C1-C6 alkyl and fluorenylmethoxycaronyl (FMOC);
R 67 is selected from the group consisting of hydrogen and
C1-C6 alkyl;
R 3 is a lower alkyl group;
R 4 is H or OH;
R 5 is H or OH;
R 4 and R 5 may be taken together to form a second bond
between C 13 and C 14;
R 6 is selected from the group consisting of benzyl,
hydroxybenzyl, alkoxybenzyl, halohydroxybenzyl,
dihalohydroxybenzyl, haloalkoxybenzyl, or dihaloalkoxybenzyl
group, B-ring heteroaromatic, substituted heteroaromatic,
B-ring (C1-C6)alkyl, (C3-C8)cycloalkyl, substituted C3-C8
cycloalkyl, substituted (C1-C6)alkyl, a group of the formula
III':
Image
and a group of the formula III'':
Image
R 7 is H or a lower alkyl group;
R 8 is H or a lower alkyl group;
R 9 is H or a lower alkyl group;
R 10 is H or a lower alkyl group;
R 11 is selected from the group consisting of H, OH, simple
alkyl, phenyl, substituted phenyl, benzyl, and substituted
benzyl;
-42-
R 15, R 16, and R 17 are each independently selected from the
group consisting of hydrogen, (C1-C6)alkyl, OR 18, halo,
NR 18 R 19 , NO2, OPO4H2, OR 19 phenyl, SCH2phenyl, CONH2, CO2H,
PO3H2, SO2R23, and ZZ;
R 18 is selected from the group consisting of hydrogen, aryl,
and C1-C6 alkyl;
R 18 is selected from the group consisting of hydrogen and
(C1-C6)alkyl;
R 19 is C1-C6 alkyl;
R 19 is selected from the group consisting of hydrogen and
(C1-C6)alkyl;
R 23 is selected from the group consisting of hydrogen and
(C1-C3)alkyl;
R 30 is hydrogen or C1-C6 alkyl;
Image
R 50 is hydrogen or ;
n is 0, 1, or 2;
p is 0, 1, or 2;
m is 0, 1, or 2;
q is 2, 3, or 4;
X is O, NH or alkylamino;
Y is C, O, NH, S, SO, SO2 or alkylamino;
Z is selected from the group consisting of -(CH2) n-,
-(CH2)p-O-(CH2)m- and (C3-C5)cycloalkyl;
ZZ is selected from the group consisting of an aromatic
group and a substituted aromatic group.
10. A process of Claim 7 wherein the solvent is
toluene.
11. A process of Claim 7 wherein Ar is aromatic or
substituted aromatic.
12. A process of Claim 7 wherein R 30 is hydrogen,
R 7 and R 8 are each methyl, X is O, Y is O, and R 50 is a group
Image
of the formula
-43-
13. A process of Claim 7 wherein R 30 is hydrogen,
one of R 7 and R 8 is methyl, X ls o, Y is O, and R 50 is a
Image
group of the formula