Lectia 7

SINTEZA COMPUȘILOR DRIMANICI ȘI

NORLABDANICI CARE CONȚIN AZOT
 12
11 16
11
15 Scheletul 20 17 13
9 14
Scheletul 1 9
12 ipotetic al 2
1 10
15
2 10 8 H 8
ipotetic al 3
4 5 6 7 labdanului 3
4 5 6 7

drimanului H
19 18
H
14 13
O
OH
CHO CHO O O
CHO OH
CHO

Many terpenes exhibit various biological activities. In a series of articles

it has been reported on the appearance of SOME NEW PROPERTIES or
anticancer THE INTENSIFICATION OF ORIGINAL ACTIVITY that accompanies
antidiabetic the introduction of nitrogen or heterocycle in the molecules of native
terpenoids. Therefore the synthesis of the nitrogen- or heterocycle -
antimalarial containing terpenic compounds is of great interest for further studies of
antiinflammatory their biological activity.
antimicrobial Herein we put into discussion the recently elaborated methods for
antibacterial preparation of :
antifungal 1. New nitrogen-containing drimane / norlabdane biologically active
compounds
anti-HIV 2. New biologically active compounds containing both drimane/ norlabdane
and heterocyclic structural units.
 !!!!
Un domeniu destul de puţin studiat
al chimiei terpenoidelor, care a luat
amploare in ultimii zece ani.

Totodată, compuşi terpenici ce

contin azot pot fi uşor transformaţi
în săruri solubile în apă, ce
facilitează studiul activităţii
biologice a acestora si rezolva
problema hidrosolubilitatii joase a
terpenilor.

Secondary LMWMs. Exemplary structures from microorganisms, plants, and

animals: (A) electron acceptors, (D) electron donors in charge-transfer complexes.

Franz Hadacek and Gert Bachmann. Low-molecular-weight metabolite systems chemistry.

Front. Environ. Sci., 04 March 2015, https://doi.org/10.3389/fenvs.2015.00012
 Synthesis of 11-aminodrim-7-ene from drimenol
1

Reagents: a. P2 O5 , DMSO, 20°C, 95%; b. NH2 OH·HCl, EtOH, Py,

95%; c. p-TsCl, Py, 90%; d. LiAlH 4 , AlCl3 , Et2 O, 50%.

Synthesis of 11-aminodrim-7-ene 5 from drimenol 1 was

accomplished in four steps.

Drimenolul (1) a fost oxidat cu pentaoxid de fosfor în DMSO, dând cu randament înalt (97%) drimenalul (2).
Drimenal oxima (3) a fost obţinută la tratarea aldehidei (2) cu clorhidratul hidroxilaminei în mediu de amestec
de etanol şi piridină. Conform datelor cromatografiei în strat subţire (CSS) produsul reacţiei reprezintă
amestecul izomerilor Z şi E ai oximei (1:5). Prin corelare cu datele din literatura a fost stabilit, ca izomerul
major are configuraţia E. Următorul pas în sinteza drimenilaminei (5) a fost reducerea oximei drimenalului (3).
La reducerea ei în diferite condiţii a fost obţinută amina (5) cu randamente mici, cuprinse între 20 şi 30%. Prin
urmare, s-a recurs la transformarea în nitrilul corespunzător (4), care ulterior a fost redus în amina (5). Dintre
multiplele metode de convertire a oximelor în nitrili care au fost testate, mai rezultativa s-a dovedit a fi: p-TsCl
în Py, randamentul nitrilului (4) constituind 90%. Produsul dorit, 11-aminodrim-7-ena (5), a fost obţinut cu un
randament de 50% la refluxarea nitrilului (4) cu LiAlH4 în Et2O în prezenţa de AlCl3 anhidru. Structura
compusului (5) a fost confirmată prin metode spectrale (IR, NMR).
 Aricu, A., Cucicova, C., Barba A., Vlad, P. F., Chemistry of Natural Compounds, 2009, № 3, p. 311-314
http://riccce20.chimie.upb.ro/#

Synthesis of 11-aminodrim-7-ene from drimenol

Reagents: e. NaBH4, CoCl2 . 6H2O, MeOH, 20oC, 91%.

Daca, insa, in calitate de reducator al nitrilului (4) este folosita NaBH4 şi CoCl2.6H2O
în metanol, a fost obţinut amestecul drimenilaminei (5) şi 7,8-dihidro-11-
aminodrimanului (6) care formează amestec de clorhidraţi solubili în apă, spectrul
IR al căruia conţine benzi la 3400, 1950, 1580, 1490 cm-1, caracteristice pentru
clorhidraţii aminelor primare. Spectrul RMN al acestui amestec denotă, că produsul
conţine clorhidraţii drimenilaminei (5) şi 7,8-dihidrodrimenilaminei (6) în raport de
2:1. Astfel, a fost sintetizată drimenilamina (5) şi amestecul ei cu 7,8-dihidro-11-
aminodrimanul (6).

The assay of biological activity of pure compound 5 and its mixture with 6 has
shown their antifungal activity.
 Synthesis of the amino- analogues of the 14,15-bisnorlabd-8α-ol-13-one

R NH2
d

H H
5 R=O 7
b 6 R=NOH

c
OH

O NH2
a d
OH OH OH

H H H

1 2 R=O 4
b 3 R=NOH

Reagents: a. KMnO4 , CH3 OCH3 , b) NH2 OH∙HCl, , c) CH 3 SO3 Si(CH3 )3, 97%, d) LiAlH 4 , THF .

In order to search the new biologically active substances and in the continuation of our work on the
synthesis of nitrogen-containing norlabdanes, a four-step synthesis of 13-amino-14,15-dinorlabd-8-
ol 4 and 13-amino-14,15-dinorlabd-8(9)-ene 7 from sclareol 1 was performed. A key-step in the
synthesis of compounds 4 and 7 is the reaction of the corresponding oxime with LiAlH4.

 . Kuchkova, K.; Aricu, A.; Secara, E.; Barba, A.; Dragalin, I.; Vlad, P.; Ungur, N. Russ. Chem. Bull., Intern. Ed., 2014, 63(9), pp.
2074-2076.
Synthesis of some new drimane d
c
and homodrimane O N-OH NH2
sesquiterpenoids containing the 3 4 5
nitrogen atom in cycle B
a or b

O CO2CH3 CO2CH3 COOH

O
2 steps c e
O N-OH N-OH
1 2 6 7
d
d

CH2-OH CH2 -OH

Reagents: a) KOH, EtOH, reflux, 3h, 98%; b) KOH, EtOH,
MW, 1.5h, 98%.; c) NH2 OH. HCl, EtOH, Py, 24h, 96-98%; d)
LiAlH4 , THF, 5h-24h, 51-60%; e) KOH, MeOH, 95%. +
N-OH O
8 9

Synthesis of some new drimane and homodrimane sesquiterpenoids containing the nitrogen atom in
cycle B is reported. The drimanic and homodrimanic oximes were prepared on the basis of ketones
derived from sclareolide. The drimanic amines were obtained by reduction of the corresponding oximes
with LiAlH4. Several attempts to reduce oximic functions from molecules of compounds 6 and 7 were
unsuccessful, probably because of steric impediments which appear in the molecules of the mentioned
homodrimanic oximes 6 and 7, but not in the molecules of drimanes.
 Lidia Lungu, Chemistry Journal of Moldova, 2015, 10(2), 58-61.
Saczewski F, Balewski Ł. Biological activities of guanidine compounds. Expert Opinion on
Therapeutic Patents , 2009 Oct;19(10):1417-48.
doi: 10.1517/13543770903216675.

BACKGROUND:
The guanidine group defines chemical and physicochemical properties of many compounds of
medical interest and guanidine-containing derivatives constitute a very important class of
therapeutic agents suitable for the treatment of a wide spectrum of diseases.

- pharmacological properties, mechanisms of action and therapeutic uses of simple guanidine

derivatives, cyclic analogues of guanidines as well as peptides, peptidomimetics and peptoids
incorporating arginine.
-interesting biological activity
-the newest developing drugs.
CONCLUSION:
Recent achievements in the synthesis of guanidine-containing molecules with diverse
chemical, biochemical and pharmacological properties make them of great importance to the
design and development of novel drugs acting at CNS, anti-inflammatory agents, inhibitors of
Na(+)/H(+) exchanger, inhibitors of NO synthase, antithrombotic, antidiabetic and
chemotherapeutic agents as well as guanidinium-based transporters and vectors.
 Synthesis of guanidine derivatives of 12-amino-11-dihomodrimane-8α-ol
and 13-amino-14,15-dinorlabd-8(9)-ene
O

O NOH NH2 NH C NH2

NH
2 steps LiAlH4
OH OH NH(Na)CN/AcOH OH
ref. 3 THF EtOH/H2O
(5:1)
1 2 3 4

OH
NOH NH2 HN C NH2
3 steps LiAlH4 NH(Na)CN/AcOH
OH ref. 4 THF EtOH/H2O
NH
(1:1)

5 6 7 8

We herein describe the synthesis of guanidine derivatives 4 and 8 of 12-amino-11-dihomodrimane-8α-ol

3 and 13-amino-14,15-dinorlabd-8(9)-ene 7, according to the scheme.
A key-step in the synthesis of compounds 4 and 8 was the reaction of the corresponding amines 3 and 7
with sodium cyanamide in ethanol/water solution, which was neutralized with acetic acid.
Dihomodrimane and 14,15-dinorlabdane guanidine – containing compounds 4 and 8 are of interest as
compounds with an increased potential of biological activity.

 A.N. Aricu, K.I. Kuchkova, A.N. Barba, E.S. Secara, I.P. Dragalin, N.D. Ungur, P.F. Vlad – Synthesis of guanidine derivatives of 12-
amino-11-dihomodrimane-8α-ol and 13-amino-14,15-dinorlabd-8(9)-ene. The XXXIV-th Romanian Chemistry Conference, Calimanesti-
Caciulata, Romania, October 4-7, 2016, p. 22.
 Synthesis of D8,9-bicyclohomofarnesenic acid guanidine derivatives from
norambreinolide
O

O OCOCH 3 OR

2 steps a c
ref . 1, 2 OH
72% 95%

1 2 3, R= Ac
b
(99%) 4, R= H
CHO COOH CONH C NH2
NH
d e
94% +

6
5 7 (54%)
CO NH C NH CO
NH
+

8 (15%)

Reagents and conditions: a. MeSO3SiMe3, CH3CN, 20°C, 5 h; b. KOH, MeOH, 20°C, 2 h; c. DMSO, P2 O5, CH2Cl2, 0°C, 10 min,
20°C, 45 min, Et3 N, 0°C, 10 min, 20°C, 45 min; d. NaClO2, NaH2 PO4‧2H2O, 2-Methyl-2-butene, t-BuOH, 20°C, 2 h; e. CDI,
.
DMF, 20°C, 1 h, then addition to a guanidine solution in DMF/dioxane (1:1), obtained from guanidine‧HCl and t-BuOK, and the
stirring, 20°C, 28 h, under Ar
In a search for new biologically active compounds, in the present scheme we describe the preparation of D8,9-
bicyclohomofarnesenic acid guanidine derivatives 7 and 8 .
Guanidine derivatives 7 and 8 were synthesized through the addition of guanidine to the activated carboxylic acid
promoted by carbonyldiimidazole (CDI). We are in the process of studying the biological effect of these molecules.
 A.N. Aricu, K.I. Kuchkova, A.N. Barba, E.S. Secara, I.P. Dragalin, N.D. Ungur, P.F. Vlad . The XXXIV-th Romanian Chemistry
Conference, Calimanesti-Caciulata, Romania, October 4-7, 2016, p. 9.
 Synthesis of nitrogen-containing homodrimanic
sesquiterpenoids from 11-dihomodrim-8(9)-en-12-one

O R N

O N O
c
a
OH +
d

H H H H
1 2 R=O 4 5
b 3 R=NOH

Molecular structure and packing

diagram of dimers in the x-ray
structure of compound 5

Reagents: a) CH3 SO 3 Si(CH 3 )3 , 97%, b) NH 2 OH .HCl, EtOH, Py; c) 86%H 3 PO 4 , d) CF3 CO2 H.

11-Dihomodriman-8-ol-12-one 1 served as starting material for obtaining the new nitrogen

containing drimanic compounds: 1,2,6-oxazine 4 and N-pyroline oxide 5 derivative, which are of
interest as potentially endowed with promising biological properties compounds.

Aricu, A., Cucicova, C., Barba A., Vlad, P. F., Chemistry of Natural Compounds, 2011, №2, p. 205- 210.
 Beckmann rearrangement of oximes 2 and 3

12 S
13
16
11 5
SOCl2 4
a 10 6
3 NH + 3 O 3 O
-2 HCl 9 7
NOH 1 1 NH -H2O 8 1 NH
O
2 4 5 6
15 14

Vezi: [10]
4 steps
Slide-ul 7
O 17
COOCH 3 COOCH 3 COOCH 3
12
16
13
O 11
5
[10] b 6
10 +
3 steps 3 3 O
9 7 O
8 1 NH 1 NH
NOH
1 3 15 14 7 8

Reagents: a) SOCl2 , dioxan, 50-60°C, 9h; b) SOCl2 , dioxan, 60-65°C, 17 h

The synthesis of new drimane and homodrimane lactams 4-8 by the Beckmann rearrangement of
the corresponding oximes 2 and 3 is described. The treatment of ketoxime 2 with thionyl chloride in
anhydrous dioxane, resulted in a mixture of isomeric lactams 4 and 6. The Beckmann
rearrangement of oxime 3 under these conditions gave a mixture of lactams 7 and 8 .

 Elena Secara , Chemistry Journal of Moldova, 2016, 11(1), 50-54.

 Synthesis, Structure and Antimicrobial Activity of Norlabdane
Compounds with Azine, Hydrazide, and Dihydrazide Fragments
O
…
O N N
O
a OH b
65% 80% OH HO

1 2 3

c
31% O O
C
NH (CH2) 4 NH
N N

OH HO
4

Reagents: a) CH3 Li, Et2 O, 20°C, 15min; b) N2 H4 .H2O, CH3 OH, D, 10h; c) N2H4 .H2 O, CH3 OH, 20°C, 48h, D, 20h

Several azines and hydrazides are known to possess high and varied biological activity, including antituberculosis
and antibacterial. We supposed that adding these fragments to the drimane scaffold can increase its biological
potential.
The starting material for synthesizing azine 3 and dihydrazide 4, 11-dihomodriman-8-ol-12-one 2 was prepared
from sclareolide 1, as described previously by us. Reaction of 2 with hydrazine hydrate in MeOH formed azine 3.
Refluxing 2 with adipic acid dihydrazide in MeOH gave dihydrazide 4, in which two ketones were condensed
through their carbonyl groups to adipic acid dihydrazide.
 A. N. Aricu, K. I. Kuchkova, A. N. Barba, I. P. Dragalin, S. G. Shova, N. Vornicu, E. K. Gorinchoi, E. S. Sekara, L. V. Lungu, M.
Niculaua, N. D. Ungur, P. F. Vlad Chemistry of Natural Compounds. 2016, Т 52, № 6, 1029-1036.
2
…

The second part of the presentation consists in preparing, from local renewable
raw materials, a series of new tetranorlabdanic compounds with triazole,
oxadiazole, thiadiazole, diazine fragments exhibiting selective biological
activity and low toxicity due to the natural origin of these substances.

N N N N N N N
N
N S O
triazole thiadiazole oxadiazole diazine
 Synthesis and structure of homodrimane sesquiterpenoids
containing 1,2,4-triazole and carbazole cycles.
H
N N
HN
O N 17
COOH COCl N
b N N 11 N
12
NH2 55 NH2 16
a 13
18 N
1 9
8 NH2
NH2
3 5 7
H H N
H
32 48 c 15 14
56 57
O

NH N

H
58
Reagents: a. (COCl)2 , C6H6 , 20oС, 1h, Δ, 1h; b. amina 23, CH2Cl2 , 20°C, 3h (58%); c. amina 24, CH2 Cl2 , 20°C, 10h, Δ,
5h, (61%)

Amides of D8,13-bicyclohomofarnesenic acid containing 1,2,4-triazole 57 and carbazole rings 58 were

synthesized in eight steps from sclareolide. Compounds were prepared by coupling the acid chloride
with the heterocyclic amines: 3-amino-1,2,4-triazole and N-aminocarbazole. Their structures were
elucidated by spectral methods and X-ray crystal structure analyses.

 Kuchkova K., Aricu A., Secara E., Barba A., Vlad P., Macaev F., Melnic E., Kravtov V., Chem. Nat. Compd., 2015,
4, p. 589-593.
 Design, synthesis, and antimicrobial activity of some novel
homodrimane sesquiterpenoids with a diazine skeleton

Reagents: а. LiAlH 4 , Et2 O, Δ, 2ore, 98%; b. Ac2 O, Py, 20°C, 2ore, 100%; c. POCl3 , Py, 0°C, 2ore, 24°C, 3ore, 96%; d.
MPFA, Et2 O, 0°C, 5ore, 65%; e. KOH, MeOH, 20°C, 2ore, 100%; f. reagentul Jones, (CH 3 )2 CO, 20°C, 3ore, 98%;g.
(COCl)2 , C6 H6 , 20ºC, 1 oră, Δ, 1oră; h. amină, CH2 Cl2 , 20ºC, 2 ore.

A comprehensive study of the synthesis and structure of new homodrimane sesquiterpenoids with diazine skeleton
is presented. This is the first synthesis of homodrimane sesquiterpenoids with diazine skeleton. At the same time, an
efficient way for the one pot bis acylation of 2-aminopyrimidine is reported. The structure of the bis acylamide was
proven unambiguously, including the single crystal X-ray structure determination.

 Kaleria Kuchkova, Aculina Aricu, Alic Barba, Pavel Vlad, Sergiu Shova, Elena Secara, Nicon Ungur, Gheorghita Zbancioc, Ionel I. Mangalagiu,
Synlett, 2013, 24, 697–700.
 Kaleria Kuchkova, Aculina Aricu, Elena Secara, Alic Barba, Pavel Vlad, Nicon Ungur, Cristina Tuchilus, Sergiu Shova, Gheorghita
Zbancioc, Ionel I. Mangalagiu – Med. Chem. Res, 2014, 23, 1559 – 1568.
 Synthesis of tetranorlabdane compounds with triazole units
NCS
O O S
O NH2 NH
N N NH
H R3 R1 H
NH2NH2*H2O
O EtOH R2
OH OH
90% EtOH
R3 R1
2 R2
1
3a R1=R3=H; R2=Me 85%
3b R1=R3=Me; R2=OH 91%

8%NaOH
N N N NH
O O
S Br S
N N

OH
OH
R3 R1
R3 R1
R2
Et3N/ Acetona R2
5a R1=R3=H; R2=Me 78%
5b R1=R3=Me; R2=OH 80% 4a R1=R3=H; R2=Me 70%
4b R1=R3=Me; R2=OH 76%

Herein we report the synthesis of some new homodrimane sesquiterpenoids with 1,2,4-triazole fragments. The
compound intermediate 2 was prepared by the reaction of sclareolide 1 with hydrazine hydrate in ethanol. The resulted
hydrazide 2 was treated with substituted aryl isothiocyanates, to yield hydrazinecarbothiamides 3a–b. The
carbothiamide 3a–b in the presence of 8% NaOH formed the corresponding tetranorlabdane compounds with triazole
units 4a–b. The S-substituted 1,3,4-triazoles 5a-b were synthesized by the coupling reaction between triazoles 4a–b
and bromoacetophenone.
 L. Lungu, A. Aricu, A. Ciocarlan, A. Barba, N. Vornicu. The XXXIV-th Romanian Chemistry Conference, Calimanesti-
Caciulata, Romania, October 4-7, 2016, p. 11.
 Synthesis of tetranorlabdane compounds with thiadiazole and
oxadiazole units
O N N N N
O
O Br O
N NH 2 S
SH S
S
H
O NH2 NH2*HCl
EtOH TMTD/ DMF
OH OH OH
90% 75% Et3N/ Acetona
85% 4
1 2 3
CDI/ THF
81%
O
O
Br N N
N NH
O O
O O

OH OH
Et 3N/ Acetone
81%
5 6

The thiadiazole and oxadiazole compounds are considered interesting heterocycles since they possess important
pharmacological activities. The results of investigations devoted to the synthesis of new homodrimane compounds
containing thiadiazole and oxadiazole structural units are reported. The homodrimane derivatives 3 and 4 with
thiadiazole units were prepared from the intermediate hydrazide 2 which was treated with the TMTD (tetramethyl
thiuram disulfide).
The homodrimane derivatives 5 and 6 with oxadiazole units were prepared from the intermediate hydrazide 2 which
was treated with the CDI (1,1′-carbonyldiimidazole).

 C. Șmigon, L. Lungu, A. Aricu, A. Ciocarlan, A. Barba, N. Vornicu. The XXXIV-th Romanian Chemistry Conference, Calimanesti-Caciulata,
Romania, October 4-7, 2016, p
 Structure confirmation
N N
O
S
N

N NH
OH
S
N
OH
OH
5b

4a

N N
O
S
S

OH

All the obtained compounds were identified and 4

characterized by IR and 1H- , 13C- NMR spectroscopic
methods, and three of them were confirmed by single
crystal X-ray diffraction.
 Studies of Biological Activity

Compound MIC (μg/ml)

Aspergillus Fusarium Penicillium Penicillium Alternaria Bacillus Pseudomonas

niger solani frequentans alternata sp. aeruginosa
chrysogenum
2 24 24 24 24 24 192 192
3a 0.125 0.125 0.125 0.125 0.125 0.064 0.064
3b >32 >32 >32 >32 >32 >256 >256
4a > 24 > 24 > 24 > 24 > 24 <192 <192
4b 0.094 0.094 0.094 0.094 0.094 0.047 0.047

5a > 24 > 24 > 24 > 24 > 24 <192 <192

5b > 32 > 32 > 32 > 32 > 32 <256 <256
3 0,032 0,032 0,032 0,032 0,032 0,094 0,094

4 > 32 > 32 > 32 > 32 > 32 <256 <256

Caspofungi 0,24 0,24 0,24 0,24 0,24 - -

n
Kanamycin - - - - - 3,5 3,5

All obtained compounds were tested for antibacterial and antifungal activity, thre of them have shown pronounced
quite activity against gram positive and gram negative bacteria and fungal strains in concentrations indicated in the
table, compared with standards.
 Synthesis of tetra- and pentanorlabdane compounds with
piridazinone units
CO 2CH3 O C6H4CH 3 CO 2CH3
O
3 steps N N
Br H
N
N
O K2CO 3/DMAA O
2 79% C6H4-CH3
3

O C6H 4-CH 3
R1
N N
O C6H 4CH3 O
4 steps R2 N N
H N
O + N
O K 2CO3/DMAA
O O
Mixture of 85% C6H 4-CH3
4 R1=Br, R2=H 6
O 7
5 R1=H, R2=Br
O C6H 4-CH 3
Br N N
O C6H 4CH3 O
4 steps N N
Starting from
1 Br
H N sclareolide a series of
N
O K 2CO 3/DMAA O
novel compounds
8 80% C6H 4-CH 3 containing both
9
norlabdanic and
O C6H 4-CH 3 piridazinone
Br
O C6H 4CH3
N N
O fragments, were
Br N N synthesized. Coupling
5 steps H N
reactions between the
N
O K 2CO3/DMAA O bromides and p-tolyl-
10 76%
11
C6H 4-CH 3 pyridazone were
performed in (DMAA)
 A. Aricu, A. Ciocarlan, L. Lungu, S. Shova, G. Zbancioc, I. Mangalagiu, N. Vornicu. Med. Chem. Res., 2016, 2016,
25(10), 2316-2323.
in the presence of
 Ciocarlan, A. Aricu, L. Lungu, C. Edu, A. Barba, S. Shova, I. I. Mangalagiu, M. D’Ambrosio, A. Nicolescu, C. potassium carbonate.
Deleanu, N. Vornicu.. Synlett, 2016 (accepted, DOI: 10.1055/s-0036-1588651).
 Structure confirmation and Biological activity

Compoun MIC (μg/ml)

d
Aspergillus Fusarium Penicillium Penicillium Alternaria Bacillus Pseudomonas
niger solani frequentans alternata sp. aeruginosa
chrysogenum
3 24 24 24 24 24 192 192
6 >32 >32 >32 >32 >32 <256 <256
7 1.5 1.5 1.5 1.5 1.5 48 48
9 >32 >32 >32 >32 >32 <256 <256
11 0.005 0.005 0.005 0.005 0.005 0.032 0.032

Caspofun 0.25 0.25 0.25 0.25 0.25 - -

gin
Kanamyc - - - - - 3 3
in

O C6H 4-CH 3
N N
O

N
N
O
Euroinvent
C6H 4-CH 3 „European Exhibition
11
of Creativity and
Innovation”, 14-16
May 2015
All obtained compounds were tested as antibacterial and antifungal activity
and comp. 11 showed very pronounced activity against gram positive and
gram negative bacteria and fungi strains in concentrations indicated in the
table, compared with standards. Due to the obtained results by method of
synthesis and biological activity of compound 11was patented.